Affinage

MLC1

Membrane protein MLC1 · UniProt Q15049

Length
377 aa
Mass
41.1 kDa
Annotated
2026-06-10
100 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MLC1 is an eight-transmembrane astrocytic membrane protein that localizes to distal astroglial processes at perivascular, subependymal, and subpial endfeet and to astrocyte-astrocyte contacts, where it organizes osmotic and volume-regulatory signaling (PMID:11254442, PMID:15892299, PMID:15367490). At the plasma membrane MLC1 assembles into higher-order complexes with the dystrophin-glycoprotein complex (DGC), interacting directly with Kir4.1, syntrophin, dystrobrevin, and caveolin-1, and partitioning into astrocytic lipid rafts (PMID:17628813, PMID:18165104, PMID:19931615); it also binds the Na,K-ATPase β1 subunit, an association favored under hypo-osmotic stress that links MLC1 to cell volume control (PMID:20926452). GlialCAM serves as the obligate chaperone that traffics MLC1 to cell junctions, and the two form homo- and hetero-complexes that, together with the ClC-2 chloride channel, constitute a functional MLC1–GlialCAM–ClC-2 unit required for proper glial-domain targeting in vivo (PMID:21624973, PMID:23793458, PMID:24647135). Functionally, MLC1 controls cell volume and osmotic homeostasis: it potentiates volume-regulated anion currents (VRAC/LRRC8) indirectly—without binding LRRC8A—by modulating ERK and LRRC8C phosphorylation, and is itself a CaMKII substrate phosphorylated upon intracellular Ca2+ release to potentiate ICl,swell (PMID:23793458, PMID:30076890, PMID:36078064). MLC1 additionally limits endosomal acidification and promotes recycling of itself and the TRPV4 channel, regulates actin remodeling through the ARP2/3 complex, stabilizes Connexin-43 gap junctions by inhibiting ERK1/2-mediated Cx43 phosphorylation, and dampens IL-1β-driven inflammatory signaling (PMID:24561067, PMID:31888684, PMID:31209783, PMID:32521795). Disease-causing MLC1 mutations cause protein misfolding, ER retention, and enhanced degradation, abolishing these functions, and MLC1 mutations cause megalencephalic leukoencephalopathy with subcortical cysts; in vivo, Mlc1-expressing perivascular astrocytes are essential for blood-brain barrier integrity (PMID:11254442, PMID:18757878, PMID:34965971).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2001 High

    Established MLC1 as a disease gene, defining the question of what cellular function a predicted eight-transmembrane protein performs whose loss causes leukoencephalopathy.

    Evidence Linkage analysis and mutation screening in MLC families

    PMID:11254442

    Open questions at the time
    • Protein function and subcellular role unknown
    • No localization or interaction data
    • Topology only predicted
  2. 2005 High

    Localized MLC1 to distal astroglial processes at perivascular, subependymal, and subpial regions, placing the protein at glial membrane interfaces and supporting a transport-related role from its even transmembrane count.

    Evidence Immunohistochemistry, in situ hybridization, and biochemical topology assays in brain

    PMID:15892299

    Open questions at the time
    • No transported substrate identified
    • Binding partners unknown
    • Functional consequence of localization untested
  3. 2004 High

    Showed MLC1 assembles into plasma-membrane complexes and that disease mutations are folding/trafficking defects, framing MLC as a conformational disease amenable to chemical rescue.

    Evidence Assembly-dependent trafficking assays and pharmacological rescue with curcumin

    PMID:15367490

    Open questions at the time
    • Identity of complex partners not defined
    • Mechanism of curcumin rescue unclear
  4. 2007 Medium

    Identified the dystrophin-glycoprotein complex as MLC1's molecular environment, with a direct MLC1-Kir4.1 interaction, connecting MLC1 to potassium and water homeostasis machinery at endfeet.

    Evidence Co-localization and immunoprecipitation in human brain tissue (idx 3); lipid-raft co-fractionation with dystroglycan, syntrophin, caveolin-1 (idx 4)

    PMID:17628813 PMID:18165104

    Open questions at the time
    • Direct vs. complex-mediated interactions not fully separated
    • Functional consequence of DGC association untested
  5. 2008 High

    Defined the molecular basis of pathogenic missense mutations as enhanced ER-associated and endo-lysosomal degradation, confirming MLC as a conformational disease rescuable by chaperone-like conditions.

    Evidence Expression in oocytes, mammalian cells, and primary cultures with low-temperature/glycerol rescue

    PMID:18757878

    Open questions at the time
    • Does not establish lost downstream function
    • Rescue not validated in vivo
  6. 2010 High

    Connected MLC1 to volume regulation by identifying a direct Na,K-ATPase-β1 interaction and showing hypo-osmotic stress drives MLC1 membrane recruitment and complex assembly.

    Evidence Yeast two-hybrid, pull-down, ouabain-affinity chromatography, hypo-osmotic stress in astrocytes

    PMID:20926452

    Open questions at the time
    • Mechanism linking complex to volume sensing not resolved
    • Ion-transport activity not directly demonstrated
  7. 2011 High

    Demonstrated MLC1 loss-of-function causes intracellular vacuolation reversible by re-expression, and that membrane localization at junctions depends on the actin cytoskeleton and ZO-1, linking MLC1 to junctional architecture.

    Evidence siRNA knockdown with rescue, co-IP with ZO-1, cytoskeletal disruption assays (idx 8); GlialCAM homo/hetero-complex and trafficking hierarchy (idx 9)

    PMID:21440627 PMID:21624973

    Open questions at the time
    • Cause of vacuolation mechanism unclear
    • Functional readout of ZO-1 interaction undefined
  8. 2013 High

    Established GlialCAM as the chaperone required for MLC1 plasma-membrane targeting and VRAC activation, providing a unifying explanation for why GLIALCAM and MLC1 mutations phenocopy each other.

    Evidence Gain/loss-of-function of GlialCAM in HeLa and astrocytes with VRAC electrophysiology and vacuolation assays

    PMID:23793458

    Open questions at the time
    • Mechanism of VRAC potentiation not yet defined
    • Direct vs. indirect channel coupling unresolved
  9. 2014 High

    Defined the in vivo MLC1–GlialCAM–ClC-2 functional axis and showed MLC1 modulates endosomal pH and recycling of itself and TRPV4, establishing roles in chloride channel regulation and endosomal protein trafficking.

    Evidence Glialcam and Mlc1 KO mice with ClC-2 electrophysiology (idx 11); endosomal pH, transferrin and TRPV4 recycling assays with mutant controls (idx 12)

    PMID:24561067 PMID:24647135

    Open questions at the time
    • How MLC1 sets endosomal pH mechanistically unknown
    • ClC-2 modulation mechanism not molecularly defined
  10. 2015 High

    Mapped the GlialCAM domains required for junction targeting, MLC1/ClC-2 interaction, and ClC-2 activation, separating the structural determinants of complex assembly from channel modulation.

    Evidence Mutagenesis with electrophysiology and biochemical interaction assays

    PMID:26033718

    Open questions at the time
    • Corresponding MLC1 interaction determinants not mapped
    • Structural model absent
  11. 2018 High

    Resolved that MLC1 potentiates VRAC indirectly through ERK signaling and LRRC8C phosphorylation rather than by binding LRRC8A, clarifying the signaling logic of MLC1's volume-regulatory effect.

    Evidence LRRC8A knockdown, VRAC electrophysiology in astrocytes and oocytes, ERK and LRRC8C phosphorylation assays

    PMID:30076890

    Open questions at the time
    • How MLC1 controls ERK activity mechanistically unknown
    • Kinase acting on LRRC8C not defined
  12. 2019 Medium

    Extended MLC1 function to actin remodeling via ARP2/3, anti-inflammatory regulation of astrocyte activation, and developmental assembly of perivascular complexes coincident with BBB maturation.

    Evidence Imaging/RNAi of actin dynamics and Arp3-Cortactin (idx 15); IL-1β stimulation and pERK/pNF-κB/pSTAT3 assays (idx 16); gliovascular unit fractionation across postnatal timepoints (idx 20)

    PMID:30684007 PMID:31209783 PMID:31888684

    Open questions at the time
    • Direct vs. signaling-mediated actin effects unresolved
    • Anti-inflammatory mechanism not molecularly defined
  13. 2020 Medium

    Showed MLC1 stabilizes Cx43 gap junctions by inhibiting ERK1/2-mediated Cx43 phosphorylation and that MLC1 drives glioblastoma stem-cell invasion via Axl signaling, broadening its roles to intercellular communication and tumor biology.

    Evidence Co-IP, phospho-Cx43 western blot, gap-junction electrophysiology (idx 17); RNAi in GSCs with in vitro/in vivo invasion assays and Axl pathway analysis (idx 18)

    PMID:32521795 PMID:33040087

    Open questions at the time
    • Mechanism by which MLC1 suppresses ERK not defined
    • Direct link between MLC1 and Axl not established
  14. 2021 High

    Demonstrated in vivo that Mlc1-expressing perivascular astrocytes are essential for blood-brain barrier integrity, connecting the cell type defined by MLC1 to endothelial junction maintenance.

    Evidence Mlc1-T2A-CreERT2 conditional astrocyte ablation with Claudin-5/VE-Cadherin imaging and BBB integrity assays

    PMID:34965971

    Open questions at the time
    • Does not isolate MLC1 protein function from astrocyte presence
    • Molecular signal to endothelium unknown
  15. 2022 High

    Identified CaMKII as the kinase that phosphorylates MLC1 upon intracellular Ca2+ release to potentiate swelling-activated chloride currents, defining a Ca2+-CaMKII-MLC1 axis coupling Ca2+ signaling to volume regulation.

    Evidence CaMKII inhibition/activation, Ca2+ imaging, and VRAC current measurement in astrocytes

    PMID:36078064

    Open questions at the time
    • Phosphorylation site(s) not mapped
    • How phosphorylation alters MLC1 activity unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The primary biochemical activity of MLC1—whether it transports ions/solutes itself or acts purely as a scaffold/regulator—remains undefined, as does the structural basis for its assembly with GlialCAM and the DGC.
  • No demonstrated direct transport function
  • No high-resolution structure of MLC1 or its complexes
  • Phosphosite-level mechanism of regulation unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0060090 molecular adaptor activity 3
Localization
GO:0005886 plasma membrane 4 GO:0005783 endoplasmic reticulum 3 GO:0005768 endosome 2
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-382551 Transport of small molecules 3
Partners
ATP1B1CAVEOLIN-1CLCN2DYSTROBREVINGLIALCAMKIR4.1SYNTROPHINZO-1
Complex memberships
MLC1-GlialCAM-ClC-2 complexNa,K-ATPase complexdystrophin-glycoprotein complex

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Mutations in MLC1 (KIAA0027), which encodes a putative membrane protein with eight predicted transmembrane domains, cause megalencephalic leukoencephalopathy with subcortical cysts (MLC). Twelve different mutations were identified including frameshifts, splice-acceptor mutations, and amino acid substitutions in predicted transmembrane domains. Linkage analysis, mutation screening of candidate gene in affected families American journal of human genetics High 11254442
2005 MLC1 protein is specifically localized in distal astroglial processes in perivascular, subependymal, and subpial regions of the brain, and contains an even number of transmembrane domains (consistent with a transport function). Immunohistochemistry and assembly-dependent trafficking assays confirmed plasma membrane localization. Immunohistochemistry, in situ hybridization, topology/assembly assays with polyclonal antibodies Journal of neuropathology and experimental neurology High 15892299
2004 MLC1 is assembled into higher molecular complexes at the plasma membrane, and disease-causing MLC1 mutations impair protein folding/trafficking; this folding defect can be corrected in vitro by curcumin (a Ca2+-ATPase inhibitor). MLC1 is expressed in neurons and astrocytes, with localization at astrocyte end-feet membranes adjacent to blood vessels and at astrocyte-astrocyte contact regions. Immunohistochemistry, in situ hybridization, assembly-dependent trafficking assays, pharmacological rescue with curcumin Human molecular genetics High 15367490
2007 MLC1 is directly associated with the dystrophin-glycoprotein complex (DGC) at astrocytic endfeet, and a direct protein interaction between MLC1 and Kir4.1 was demonstrated by immunoprecipitation. In MLC brain tissue, absence of MLC1 correlates with altered expression of several DGC proteins. Immunohistochemistry, co-localization, immunoprecipitation Acta neuropathologica Medium 17628813
2007 MLC1 membrane-associated component (60-64 kDa) localizes in astrocytic lipid rafts together with dystroglycan, syntrophin, and caveolin-1, and co-fractionates with the DGC in whole rat brain tissue. In human brain, MLC1 co-localizes with dystroglycan and syntrophin in astrocyte processes and ependymal cells. Lipid raft fractionation, co-fractionation assays, immunofluorescence, polyclonal antibody characterization Molecular and cellular neurosciences Medium 18165104
2008 Most disease-causing MLC1 missense mutations dramatically reduce total and plasma membrane MLC1 expression levels, due to increased ER-associated degradation and endo-lysosomal-associated degradation. The expression defect of mutant MLC1 proteins can be rescued by low temperature and glycerol (chemical chaperone), placing MLC in the class of conformational diseases. Xenopus oocyte expression, mammalian cell expression, primary rat astrocyte and human monocyte cultures, pharmacological rescue assays, biochemical/imaging methods Human molecular genetics High 18757878
2009 MLC1 intracellular domains interact with DGC proteins syntrophin, dystrobrevin, Kir4.1, and caveolin-1 (pull-down assays). MLC1 is expressed in intracellular vesicles and ER and undergoes caveolae/raft-mediated endocytosis. Inhibition of endocytosis and PKA/PKC-mediated MLC1 phosphorylation favor membrane-associated MLC1 expression. Pull-down assays, co-fractionation, immunostaining, subcellular fractionation, pharmacological modulation of caveolin-mediated trafficking Neurobiology of disease Medium 19931615
2010 The β1 subunit of the Na,K-ATPase pump directly interacts with MLC1 in brain astrocytes, identified by yeast two-hybrid screening with the NH2-MLC1 domain as bait, confirmed by pull-downs, co-fractionation, and immunofluorescence. MLC1 was isolated in a multiprotein complex with Na,K-ATPase, Kir4.1, syntrophin, and dystrobrevin by ouabain-affinity chromatography. Hypo-osmotic conditions increase MLC1 membrane expression and favor MLC1/Na,K-ATPase-β1 association, suggesting MLC1 is involved in osmotic control and volume regulation. Yeast two-hybrid, pull-down, co-fractionation, immunofluorescence, ouabain-affinity chromatography, hypo-osmotic stress experiments Human molecular genetics High 20926452
2011 Knockdown of MLC1 in primary rat astrocytes results in the appearance of intracellular vacuoles, which is reversed by co-expression of human MLC1. MLC1 localization in cell-cell contacts depends on the actin cytoskeleton (disrupted by actin-modifying agents but not by disruption of microtubules or GFAP). MLC1 and ZO-1 co-localize and co-immunoprecipitate specifically in human tissues. siRNA knockdown, rescue by human MLC1 re-expression, co-immunoprecipitation, actin/microtubule disruption assays, EM immunostaining Neurobiology of disease High 21440627
2011 MLC1 and GlialCAM form homo- and hetero-complexes. MLC-causing mutations in GLIALCAM primarily reduce formation of GlialCAM homo-complexes, impairing trafficking of GlialCAM to cell junctions and thereby also affecting MLC1 trafficking. The S69L MLC1 missense mutation reduces MLC1 protein stability and levels in brain to almost undetectable, while GlialCAM expression and localization are largely unaffected by loss of MLC1. Human post-mortem brain analysis, in vitro primary astrocyte and heterologous cell experiments, co-immunoprecipitation, biochemical stability assays Human molecular genetics High 21624973
2013 GlialCAM acts as a chaperone for MLC1: GlialCAM ablation causes intracellular accumulation and reduced plasma membrane expression of MLC1. GlialCAM over-expression rescues stability of mutant MLC1 variants. Reduction in GlialCAM expression results in defective activation of volume-regulated anion currents (VRAC) and increased vacuolation, phenocopying MLC1 mutations. Over-expression of GlialCAM together with MLC1 containing MLC-related mutations can reactivate VRAC currents and reverse vacuolation. Gain- and loss-of-function of GlialCAM in HeLa cells and primary astrocytes, electrophysiology (VRAC currents), vacuolation assays, biochemical stability assays Human molecular genetics High 23793458
2014 In GlialCAM and Mlc1 loss-of-function mouse models with myelin vacuolization: GlialCAM is important for targeting MLC1 and ClC-2 to specialized glial domains in vivo and for modifying ClC-2 biophysical properties in oligodendrocytes. MLC1 is crucial for proper localization of GlialCAM and ClC-2 and for modifying ClC-2 currents. ClC-2 is not necessary for MLC1 and GlialCAM localization. This reveals an MLC1–GlialCAM–ClC-2 functional relationship in vivo. Knock-out mouse models (Glialcam and Mlc1), electrophysiology (ClC-2 biophysical characterization), immunofluorescence localization in brain Nature communications High 24647135
2014 MLC1 modulates endosomal pH and protein trafficking in astrocytes: wild-type MLC1 limits early endosomal acidification and stimulates protein recycling (transferrin recycling assay). MLC1 is abundantly expressed in early (EEA1+, Rab5+) and recycling (Rab11+) endosomes and traffics to the plasma membrane via recycling endosomes during hypo-osmotic stress. MLC1 also favors recycling of TRPV4 cation channel to the plasma membrane, which cooperates with MLC1 to activate calcium influx during hypo-osmotic stress. All disease-causing MLC1 mutations fail to influence endosomal pH and protein recycling. Biochemical, proteomic, and imaging analyses; FITC-dextran pH measurement; transferrin recycling assay; endosome marker co-localization; hypo-osmotic stress experiments in astrocytoma cells Neurobiology of disease High 24561067
2015 The extracellular domain of GlialCAM is necessary for targeting to cell junctions and for interactions with itself, MLC1, and ClC-2. The C-terminus of GlialCAM is required for junction targeting but not for biochemical interaction. The first three residues of the GlialCAM transmembrane segment are required for GlialCAM-mediated ClC-2 activation but not for targeting or interaction with MLC1. Mutagenesis, functional electrophysiology, biochemical interaction assays (co-immunoprecipitation), cell junction targeting assays The Journal of physiology High 26033718
2018 MLC1 and LRRC8A (main subunit of VRAC) are functionally linked: MLC1 cannot potentiate VRAC currents when LRRC8A is knocked down. However, LRRC8A and MLC1 do not co-localize or interact directly, and MLC1 does not potentiate LRRC8-mediated VRAC currents in Xenopus oocytes, indicating VRAC modulation by MLC1 is indirect. MLC1 overexpression decreases ERK phosphorylation; loss of MLC1 increases ERK phosphorylation. Changes in MLC1 levels alter phosphorylation state of VRAC subunit LRRC8C. LRRC8A knockdown, VRAC electrophysiology in astrocytes and Xenopus oocytes, co-localization/co-immunoprecipitation (negative for direct interaction), ERK phosphorylation assays, LRRC8C phosphorylation assays Neurobiology of disease High 30076890
2019 Wild-type MLC1 plasma membrane localization is critical for actin dynamics: MLC1 overexpression induces filopodia formation and suppresses cell motility. Knockdown of Mlc1 induces Arp3-Cortactin interaction, lamellipodia formation, and increased membrane ruffling in astrocytes, implicating MLC1 in regulation of actin remodeling via the ARP2/3 complex. Patient-derived MLC1 mutants are trapped in the ER and do not affect morphology or motility. Confocal and live cell imaging, RNAi knockdown, co-immunoprecipitation, surface biotinylation, overexpression of wild-type and mutant MLC1 Molecular brain Medium 31888684
2019 MLC1 inhibits astrocyte activation by down-regulating IL-1β-induced inflammatory signals (pERK, pNF-κB). IL-1β stimulates wild-type MLC1 plasma membrane expression. Wild-type MLC1 expression reduces levels of astrogliosis marker pSTAT3. MLC1 is upregulated in demyelinating/remyelinating cerebellar organotypic cultures during recovery phases, suggesting MLC1 contributes to restoring astrocyte homeostasis after inflammation. Human brain tissue analysis (MS, Alzheimer's, CJD), astrocytoma lines overexpressing WT or mutant MLC1, primary astrocytes from control and Mlc1 KO mice, IL-1β stimulation, western blot for pERK/pNF-kB/pSTAT3, cerebellar organotypic culture model Molecular neurobiology Medium 31209783
2020 Wild-type MLC1 expression favors gap junction intercellular communication by inhibiting ERK1/2-mediated Cx43 phosphorylation and increasing Cx43 gap-junction stability in astrocytes. Mutant MLC1 fails to regulate Cx43. This was shown using biochemical and electrophysiological techniques in astrocytoma cells. Biochemical assays (co-immunoprecipitation, western blot for phospho-Cx43), electrophysiology (gap junction conductance), overexpression of wild-type vs. pathological mutant MLC1 Cells Medium 32521795
2020 Genetic inhibition of MLC1 in glioblastoma stem-like cells (GSCs) using RNAi results in diminished growth and invasion in vitro and impaired tumor initiation and progression in vivo. Biochemical assays identify the receptor tyrosine kinase Axl and its intracellular signaling effectors as important downstream mediators of MLC1-controlled invasive growth. RNAi-mediated gene silencing in GSCs, in vitro growth/invasion assays, in vivo tumor initiation model, biochemical assays for Axl signaling Oncogene Medium 33040087
2021 Ablation of Mlc1-expressing perivascular astrocytes (PAs) using a Mlc1-T2A-CreERT2 knock-in mouse causes severe defects in blood-brain barrier (BBB) integrity, resulting in premature death. PA loss causes aberrant localization of Claudin-5 and VE-Cadherin in endothelial cell junctions and robust microgliosis, demonstrating that Mlc1-expressing PAs are essential for endothelial barrier integrity. Mlc1-T2A-CreERT2 knock-in mouse model, conditional PA ablation, immunofluorescence for tight junction proteins (Claudin-5, VE-Cadherin), BBB integrity assays, histology The Journal of neuroscience High 34965971
2019 MLC1 and GlialCAM are enriched and assembled into mature complexes in astrocyte perivascular endfeet between postnatal days 10 and 15, after Aquaporin 4 formation, correlating with increased expression of BBB components Claudin-5 and P-gP. This was established using purified gliovascular units from postnatal mouse brain. Purified gliovascular units, western blot, immunofluorescence across postnatal timepoints Brain structure & function Medium 30684007
2022 MLC1 is a substrate of Ca2+/Calmodulin-dependent protein kinase II (CaMKII): MLC1 phosphorylation by CaMKII occurs in response to intracellular Ca2+ release and potentiates VRAC-mediated chloride currents (ICl,swell) in astrocytes. This links volume regulation to Ca2+ signaling via CaMKII-MLC1 axis. Molecular, biochemical, proteomic, electrophysiological, and imaging techniques; CaMKII inhibition/activation; Ca2+ imaging; VRAC current measurement Cells High 36078064

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 A GIT1/PIX/Rac/PAK signaling module regulates spine morphogenesis and synapse formation through MLC. The Journal of neuroscience : the official journal of the Society for Neuroscience 284 15800193
1998 Somatic hypermutation, clonal diversity, and preferential expression of the VH 51p1/VL kv325 immunoglobulin gene combination in hepatitis C virus-associated immunocytomas. Blood 221 9516143
2001 Mutations of MLC1 (KIAA0027), encoding a putative membrane protein, cause megalencephalic leukoencephalopathy with subcortical cysts. American journal of human genetics 218 11254442
2001 Differential effect of MLC kinase in TNF-alpha-induced endothelial cell apoptosis and barrier dysfunction. American journal of physiology. Lung cellular and molecular physiology 186 11350795
2020 Resistive Random Access Memory (RRAM): an Overview of Materials, Switching Mechanism, Performance, Multilevel Cell (mlc) Storage, Modeling, and Applications. Nanoscale research letters 156 32323059
2013 ARF1 regulates the Rho/MLC pathway to control EGF-dependent breast cancer cell invasion. Molecular biology of the cell 118 24196838
2013 ABangle: characterising the VH-VL orientation in antibodies. Protein engineering, design & selection : PEDS 104 23708320
1999 PKC-dependent regulation of transepithelial resistance: roles of MLC and MLC kinase. The American journal of physiology 102 10484342
2014 Disrupting MLC1 and GlialCAM and ClC-2 interactions in leukodystrophy entails glial chloride channel dysfunction. Nature communications 101 24647135
2013 cAMP signaling regulates platelet myosin light chain (MLC) phosphorylation and shape change through targeting the RhoA-Rho kinase-MLC phosphatase signaling pathway. Blood 99 24100445
2001 The Escherichia coli glucose transporter enzyme IICB(Glc) recruits the global repressor Mlc. The EMBO journal 98 11157755
1998 Expression of ptsG, the gene for the major glucose PTS transporter in Escherichia coli, is repressed by Mlc and induced by growth on glucose. Molecular microbiology 93 9767573
2005 MLC1: a novel protein in distal astroglial processes. Journal of neuropathology and experimental neurology 88 15892299
2011 Molecular mechanisms of MLC1 and GLIALCAM mutations in megalencephalic leukoencephalopathy with subcortical cysts. Human molecular genetics 86 21624973
1997 Myeloma VL and VH gene sequences reveal a complementary imprint of antigen selection in tumor cells. Blood 86 8978295
2018 Naringin attenuates MLC phosphorylation and NF-κB activation to protect sepsis-induced intestinal injury via RhoA/ROCK pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 84 29635128
2021 AAPM Task Group 264: The safe clinical implementation of MLC tracking in radiotherapy. Medical physics 79 33260251
2003 Hyperosmotic stress activates Rho: differential involvement in Rho kinase-dependent MLC phosphorylation and NKCC activation. American journal of physiology. Cell physiology 79 12748065
2006 The RhoA/ROCK-I/MLC pathway is involved in the ethanol-induced apoptosis by anoikis in astrocytes. Journal of cell science 77 16390872
2004 Localization and functional analyses of the MLC1 protein involved in megalencephalic leukoencephalopathy with subcortical cysts. Human molecular genetics 77 15367490
2002 p38 MAPK activation by TGF-beta1 increases MLC phosphorylation and endothelial monolayer permeability. American journal of physiology. Lung cellular and molecular physiology 77 11741826
1983 Responses of neurons in VPL and VPL-VL region of the cat to algesic stimulation of muscle and tendon. Journal of neurophysiology 75 6834092
1999 Expression of the phosphotransferase system both mediates and is mediated by Mlc regulation in Escherichia coli. Molecular microbiology 71 10411743
1984 VL-VH expression by monoclonal antibodies recognizing avian lysozyme. Journal of immunology (Baltimore, Md. : 1950) 68 6418816
1999 Intrabody construction and expression. I. The critical role of VL domain stability. Journal of molecular biology 63 10518947
2011 Knockdown of MLC1 in primary astrocytes causes cell vacuolation: a MLC disease cell model. Neurobiology of disease 61 21440627
2012 Germline VH/VL pairing in antibodies. Protein engineering, design & selection : PEDS 58 22802295
2004 Indian Agarwal megalencephalic leukodystrophy with cysts is caused by a common MLC1 mutation. Neurology 56 15037685
2013 Insights into MLC pathogenesis: GlialCAM is an MLC1 chaperone required for proper activation of volume-regulated anion currents. Human molecular genetics 55 23793458
2011 Catabolic regulation analysis of Escherichia coli and its crp, mlc, mgsA, pgi and ptsG mutants. Microbial cell factories 54 21831320
2010 The beta1 subunit of the Na,K-ATPase pump interacts with megalencephalic leucoencephalopathy with subcortical cysts protein 1 (MLC1) in brain astrocytes: new insights into MLC pathogenesis. Human molecular genetics 54 20926452
2008 Molecular pathogenesis of megalencephalic leukoencephalopathy with subcortical cysts: mutations in MLC1 cause folding defects. Human molecular genetics 54 18757878
1999 Purification of Mlc and analysis of its effects on the pts expression in Escherichia coli. The Journal of biological chemistry 53 10464268
2016 Redirecting Specificity of T cells Using the Sleeping Beauty System to Express Chimeric Antigen Receptors by Mix-and-Matching of VL and VH Domains Targeting CD123+ Tumors. PloS one 52 27548616
2007 MLC1 is associated with the dystrophin-glycoprotein complex at astrocytic endfeet. Acta neuropathologica 51 17628813
1993 Role of mouse VH10 and VL gene segments in the specific binding of antibody to Z-DNA, analyzed with recombinant single chain Fv molecules. Journal of immunology (Baltimore, Md. : 1950) 51 8419479
2020 Lycium barbarum polysaccharides ameliorate intestinal barrier dysfunction and inflammation through the MLCK-MLC signaling pathway in Caco-2 cells. Food & function 50 32314770
2003 The brain-specific protein MLC1 implicated in megalencephalic leukoencephalopathy with subcortical cysts is expressed in glial cells in the murine brain. Glia 49 14603469
2015 Prediction of VH-VL domain orientation for antibody variable domain modeling. Proteins 48 25641019
2007 Expression patterns of MLC1 protein in the central and peripheral nervous systems. Neurobiology of disease 48 17434314
2016 Aryl Hydrocarbon Receptor Activation in Intestinal Obstruction Ameliorates Intestinal Barrier Dysfunction Via Suppression of MLCK-MLC Phosphorylation Pathway. Shock (Augusta, Ga.) 47 26939041
2006 Megalencephalic leukoencephalopathy with subcortical cysts: an update and extended mutation analysis of MLC1. Human mutation 47 16652334
2017 Metformin regulates tight junction of intestinal epithelial cells via MLCK-MLC signaling pathway. European review for medical and pharmacological sciences 46 29228440
2019 The Siderophore Transporter Sit1 Determines Susceptibility to the Antifungal VL-2397. Antimicrobial agents and chemotherapy 45 31405865
2006 Characterization of a new virulent phage (MLC-A) of Lactobacillus paracasei. Journal of dairy science 44 16772557
1996 Interaction between clenbuterol and run training: effects on exercise performance and MLC isoform content. Journal of applied physiology (Bethesda, Md. : 1985) 44 8964739
2019 Doxorubicin Promotes Migration and Invasion of Breast Cancer Cells through the Upregulation of the RhoA/MLC Pathway. Journal of breast cancer 42 31281722
2008 Analyses of Mlc-IIBGlc interaction and a plausible molecular mechanism of Mlc inactivation by membrane sequestration. Proceedings of the National Academy of Sciences of the United States of America 42 18319344
2007 Biochemical characterization of MLC1 protein in astrocytes and its association with the dystrophin-glycoprotein complex. Molecular and cellular neurosciences 42 18165104
2005 MLC1 gene is associated with schizophrenia and bipolar disorder in Southern India. Biological psychiatry 39 15992519
1990 VH and VL gene usage by murine IgG antibodies that bind autologous insulin. Journal of immunology (Baltimore, Md. : 1950) 38 2109009
2003 Clinical and genetic heterogeneity in megalencephalic leukoencephalopathy with subcortical cysts (MLC). Neuropediatrics 36 12973664
2000 Amplification of IgG VH and VL (Fab) from single human plasma cells and B cells. Nucleic acids research 36 11024187
2018 GlialCAM/MLC1 modulates LRRC8/VRAC currents in an indirect manner: Implications for megalencephalic leukoencephalopathy. Neurobiology of disease 35 30076890
2015 MLC1 protein: a likely link between leukodystrophies and brain channelopathies. Frontiers in cellular neuroscience 35 25883547
2009 MLC1 trafficking and membrane expression in astrocytes: role of caveolin-1 and phosphorylation. Neurobiology of disease 35 19931615
2018 Effect of VH-VL Families in Pertuzumab and Trastuzumab Recombinant Production, Her2 and FcγIIA Binding. Frontiers in immunology 33 29593727
2021 Mlc1-Expressing Perivascular Astrocytes Promote Blood-Brain Barrier Integrity. The Journal of neuroscience : the official journal of the Society for Neuroscience 32 34965971
2020 MLC tracking for lung SABR is feasible, efficient and delivers high-precision target dose and lower normal tissue dose. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 32 33152399
2017 The LPI/GPR55 axis enhances human breast cancer cell migration via HBXIP and p-MLC signaling. Acta pharmacologica Sinica 32 29188802
2022 GLP-1 RA Improves Diabetic Retinopathy by Protecting the Blood-Retinal Barrier through GLP-1R-ROCK-p-MLC Signaling Pathway. Journal of diabetes research 31 36387940
2021 Baicalin attenuates angiotensin II-induced blood pressure elevation and modulates MLCK/p-MLC signaling pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 28 34492423
2019 Postnatal development of the astrocyte perivascular MLC1/GlialCAM complex defines a temporal window for the gliovascular unit maturation. Brain structure & function 28 30684007
2017 O-GlcNAcylation promotes migration and invasion in human ovarian cancer cells via the RhoA/ROCK/MLC pathway. Molecular medicine reports 28 28259907
2006 Vacuolating megalencephalic leukoencephalopathy with subcortical cysts: functional studies of novel variants in MLC1. Human mutation 28 16470554
2018 RhoA/MLC signaling pathway is involved in Δ⁹-tetrahydrocannabinol-impaired placental angiogenesis. Toxicology letters 27 29307655
2017 cGMP signaling inhibits platelet shape change through regulation of the RhoA-Rho Kinase-MLC phosphatase signaling pathway. Journal of thrombosis and haemostasis : JTH 27 28509344
1989 Identification of the functional promoter regions in the human gene encoding the myosin alkali light chains MLC1 and MLC3 of fast skeletal muscle. The Journal of biological chemistry 27 2777779
2016 Honokiol inhibits migration of renal cell carcinoma through activation of RhoA/ROCK/MLC signaling pathway. International journal of oncology 25 27633759
2012 A new carbon catabolite repression mutation of Escherichia coli, mlc∗, and its use for producing isobutanol. Journal of bioscience and bioengineering 25 22561880
2022 Perlecan Improves Blood Spinal Cord Barrier Repair Through the Integrin β1/ROCK/MLC Pathway After Spinal Cord Injury. Molecular neurobiology 24 36216996
2020 A facile technology for the high-throughput sequencing of the paired VH:VL and TCRβ:TCRα repertoires. Science advances 24 32426460
2019 Megalencephalic Leukoencephalopathy with Subcortical Cysts Protein-1 (MLC1) Counteracts Astrocyte Activation in Response to Inflammatory Signals. Molecular neurobiology 24 31209783
2015 Melatonin Attenuates Aortic Endothelial Permeability and Arteriosclerosis in Streptozotocin-Induced Diabetic Rats: Possible Role of MLCK- and MLCP-Dependent MLC Phosphorylation. Journal of cardiovascular pharmacology and therapeutics 23 25944844
2014 Megalencephalic leukoencephalopathy with subcortical cysts protein-1 modulates endosomal pH and protein trafficking in astrocytes: relevance to MLC disease pathogenesis. Neurobiology of disease 23 24561067
2007 MLC1 polymorphisms are specifically associated with periodic catatonia, a subgroup of chronic schizophrenia. Biological psychiatry 23 17210142
2020 An Insight into the Current Perspective and Potential Drug Targets for Visceral Leishmaniasis (VL). Current drug targets 22 32321399
2020 Megalencephalic Leukoencephalopathy with Subcortical Cysts Disease-Linked MLC1 Protein Favors Gap-Junction Intercellular Communication by Regulating Connexin 43 Trafficking in Astrocytes. Cells 21 32521795
2017 Inhibition of Rho kinase protects against colitis in mice by attenuating intestinal epithelial barrier dysfunction via MLC and the NF-κB pathway. International journal of molecular medicine 21 29115372
1998 Functions of the Caenorhabditis elegans regulatory myosin light chain genes mlc-1 and mlc-2. Genetics 21 9799259
2023 Heat-Killed Lacticaseibacillus paracasei Repairs Lipopolysaccharide-Induced Intestinal Epithelial Barrier Damage via MLCK/MLC Pathway Activation. Nutrients 20 37049598
2019 Plasma membrane localization of MLC1 regulates cellular morphology and motility. Molecular brain 20 31888684
2015 Structural determinants of interaction, trafficking and function in the ClC-2/MLC1 subunit GlialCAM involved in leukodystrophy. The Journal of physiology 20 26033718
2008 The potential role of MLC phosphatase and MAPK signalling in the pathogenesis of vascular dysfunction in heart failure. Journal of cellular and molecular medicine 20 19120700
2018 IL-6 increases podocyte motility via MLC-mediated focal adhesion impairment and cytoskeleton disassembly. Journal of cellular physiology 19 29574897
2003 Sequence diversity of KIAA0027/MLC1: are megalencephalic leukoencephalopathy and schizophrenia allelic disorders? Human mutation 19 12497630
2021 Porcine Sapovirus-Induced Tight Junction Dissociation via Activation of RhoA/ROCK/MLC Signaling Pathway. Journal of virology 18 33692204
2013 DEK depletion negatively regulates Rho/ROCK/MLC pathway in non-small cell lung cancer. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 18 23571382
1996 Modular elements of the MLC 1f/3f locus confer fiber-specific transcription regulation in transgenic mice. Developmental genetics 18 8900048
2018 The C. elegans BRCA2-ALP/Enigma Complex Regulates Axon Regeneration via a Rho GTPase-ROCK-MLC Phosphorylation Pathway. Cell reports 17 30110643
2000 Expression, refolding, and ferritin-binding activity of the isolated VL-domain of monoclonal antibody F11. Biochemistry. Biokhimiia 16 11042491
1985 Suppression of human NK cell cytotoxicity by an MLC-Generated cell population. Journal of immunology (Baltimore, Md. : 1950) 16 3155463
2022 The CaMKII/MLC1 Axis Confers Ca2+-Dependence to Volume-Regulated Anion Channels (VRAC) in Astrocytes. Cells 15 36078064
2021 Designing of a Novel Fusion Protein Vaccine Candidate Against Human Visceral Leishmaniasis (VL) Using Immunoinformatics and Structural Approaches. International journal of peptide research and therapeutics 15 33935610
2020 NMMHC IIA Inhibition Ameliorates Cerebral Ischemic/Reperfusion-Induced Neuronal Apoptosis Through Caspase-3/ROCK1/MLC Pathway. Drug design, development and therapy 15 32021088
2020 Megalencephalic leukoencephalopathy with subcortical cysts 1 (MLC1) promotes glioblastoma cell invasion in the brain microenvironment. Oncogene 15 33040087
1993 Conservation of alternative splicing and genomic organization of the myosin alkali light-chain (Mlc1) gene among Drosophila species. Molecular biology and evolution 15 8355600
2023 Gastrodin attenuates angiotensin II-induced vascular contraction and MLCK/p-MLC2 pathway activation. Pharmaceutical biology 14 37211627
2023 Inhibition of UTX/KDM6A improves recovery of spinal cord injury by attenuating BSCB permeability and macrophage infiltration through the MLCK/p-MLC pathway. Journal of neuroinflammation 14 37951955
2002 An extra human chromosome 21 reduces mlc-2a expression in chimeric mice and Down syndrome. Biochemical and biophysical research communications 14 12083776

Missed literature

Know a paper Affinage missed for MLC1? Flag it for the maintainers and the community.

No submissions yet.