Affinage

MAP2

Microtubule-associated protein 2 · UniProt P11137

Round 2 corrected
Length
1827 aa
Mass
199.5 kDa
Annotated
2026-04-28
130 papers in source corpus 38 papers cited in narrative 38 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MAP2 is a neuron-enriched microtubule-associated protein that orchestrates dendritic cytoskeletal architecture by promoting microtubule polymerization, nucleation, stabilization, and bundling through a C-terminal repeat domain, while also cross-linking microtubules to neurofilaments and actin filaments (PMID:3142041, PMID:1487506, PMID:3045269, PMID:2115775). Its microtubule-binding affinity is bidirectionally regulated by phosphorylation: cdc2, MARK, GSK3β, and PKA phosphorylation within or near the repeat domain detach MAP2 from microtubules and redirect it toward actin-rich compartments, whereas NMDA receptor–activated calcineurin-mediated dephosphorylation restores microtubule association (PMID:11029056, PMID:2169265, PMID:8789950, PMID:10542369). Beyond cytoskeletal regulation, MAP2 functions as an A-kinase anchoring protein (AKAP) that recruits PKA-RIIβ to dendrites—required for cAMP/CREB signaling and contextual fear memory—and directly binds the α1 subunit of L-type Ca²⁺ channels independently of microtubules (PMID:12163474, PMID:12763072, PMID:10514522). Its mRNA is targeted to dendrites via a 640-nucleotide cis-acting element in the 3′ UTR, enabling local translation, while high-molecular-weight isoforms (MAP2a/b) contain a projection domain that determines inter-microtubule spacing, dendritic morphology, and lipid binding absent from the embryonic MAP2c splice variant (PMID:10516301, PMID:2770869, PMID:8868472).

Mechanistic history

Synthesis pass · year-by-year structured walk · 25 steps
  1. 1984 High

    Establishing MAP2 as a dendrite-specific cytoskeletal protein resolved the question of whether microtubule-associated proteins showed compartmental specificity in neurons, revealing MAP2 localizes to dendrites and postsynaptic densities but not axons.

    Evidence Immunocytochemistry and immunoelectron microscopy with monoclonal antibodies on brain tissue

    PMID:6699682

    Open questions at the time
    • Mechanism of dendritic restriction unknown at this stage
    • Whether MAP2 has functions independent of microtubules at postsynaptic densities was unresolved
  2. 1984 High

    Demonstrating that phosphorylation reduces MAP2–microtubule affinity in a dose-dependent manner established phosphorylation as a regulatory switch for MAP2 function, opening the question of which kinases and phosphatases operate in vivo.

    Evidence In vitro phosphorylation by co-purifying kinase; taxol-stabilized microtubule binding and polymerization kinetics

    PMID:6146522

    Open questions at the time
    • Identity of the endogenous kinase unknown
    • In vivo relevance not yet demonstrated
  3. 1988 High

    Mapping the microtubule-binding domain to the C-terminal 18-amino-acid repeats defined the minimal structural unit for MAP2–tubulin interaction and revealed domain architecture shared with tau.

    Evidence In vitro translation of MAP2 subcloned fragments followed by microtubule co-purification cycles; cDNA sequencing

    PMID:3142041

    Open questions at the time
    • Whether flanking sequences contribute to binding strength was untested
    • Structural basis of repeat–tubulin contact unresolved
  4. 1988 High

    Discovery that MAP2 mRNA is dendritically localized provided a mechanism for dendritic MAP2 protein enrichment through local translation, complementing protein-level localization studies and raising the question of what cis-elements direct the mRNA.

    Evidence In situ hybridization with specific cDNA probes on developing brain tissue

    PMID:3200318

    Open questions at the time
    • cis-acting targeting element not yet identified
    • Whether local translation is activity-regulated was unknown
  5. 1988 High

    Demonstrating that MAP2 cross-links microtubules to neurofilaments in dendrites expanded its role from microtubule stabilizer to an integrator of the dendritic cytoskeletal network.

    Evidence Quick-freeze deep-etch immunoEM in vivo; in vitro reconstitution with neurofilament L protein

    PMID:3045269

    Open questions at the time
    • Binding site on neurofilament L not mapped
    • Regulation of cross-linking activity unknown
  6. 1989 High

    Identification of the MAP2c splice variant lacking 1,342 aa of the projection domain, and demonstration that high-molecular-weight MAP2a/b but not MAP2c mRNA is dendritically targeted, linked alternative splicing to both isoform-specific architecture and mRNA localization.

    Evidence cDNA cloning/sequencing; in situ hybridization for MAP2c mRNA; EM of reconstituted microtubules

    PMID:2770869

    Open questions at the time
    • Developmental regulation of splicing switch uncharacterized
    • Projection domain contribution to inter-microtubule spacing not quantified
  7. 1989 High

    Microinjection tracking showed MAP2 protein enters both axons and dendrites but is selectively retained in dendrites via cytoskeletal binding, establishing differential retention rather than sorting as the compartmentalization mechanism.

    Evidence Microinjection of biotin-labeled MAP2 into spinal cord neurons; immunoEM with detergent extraction

    PMID:2657741

    Open questions at the time
    • What makes dendritic microtubules preferentially bind MAP2 was not determined
    • Whether phosphorylation state influences compartmental retention was untested
  8. 1990 High

    The tubulin-binding repeats were shown to also bind actin, revealing MAP2 as a bifunctional cytoskeletal linker and raising the question of how microtubule versus actin association is regulated.

    Evidence Affinity chromatography of G-actin on synthetic peptide; F-actin co-sedimentation

    PMID:2115775

    Open questions at the time
    • Whether microtubule and actin binding are mutually exclusive was unclear
    • In vivo significance of actin binding not demonstrated
  9. 1990 High

    NMDA receptor activation was shown to rapidly dephosphorylate MAP2 via calcineurin, linking synaptic activity to microtubule regulation and identifying the first physiological signal controlling MAP2 phosphorylation state.

    Evidence 32P-orthophosphate labeling of hippocampal slices; NMDA antagonist pharmacology

    PMID:2169265

    Open questions at the time
    • Specific phosphorylation sites dephosphorylated by calcineurin not mapped
    • Functional consequences for microtubule stability not directly measured
  10. 1992 High

    Gain-of-function expression in non-neuronal cells proved MAP2 is sufficient to stabilize microtubules against depolymerizing agents, bundle them independently of the MTOC, and impart structural stiffness—core functions for dendritic architecture.

    Evidence MAP2/MAP2c cDNA transfection into fibroblasts; drug resistance assays; acetylated tubulin staining; immunofluorescence

    PMID:1338311 PMID:1487506

    Open questions at the time
    • How bundling is coordinated with other dendritic MAPs in vivo unknown
    • Whether MAP2 stiffness is modulated by post-translational modifications untested
  11. 1993 High

    Photoactivation studies revealed MAP2c-bundled microtubules have extremely low internal tubulin exchange yet retain assembly-competent ends, explaining how MAP2 preserves stable dendritic microtubule cores while permitting dynamic growth.

    Evidence Photoactivation of caged fluorescein-tubulin in MAP2c-transfected fibroblasts; biotin-tubulin microinjection

    PMID:8421058

    Open questions at the time
    • Whether this dynamic end assembly is regulated by MAP2 phosphorylation was not tested
  12. 1994 High

    Systematic deletion mutagenesis established that efficient microtubule binding requires the repeat domain plus flanking proline-rich sequences, and that binding strength correlates with bundling capacity and process outgrowth.

    Evidence Series of MAP2c deletion mutants transfected into non-neuronal cells; immunofluorescence and process outgrowth assays

    PMID:7699010

    Open questions at the time
    • Structural basis of flanking region contribution unresolved
    • Whether post-translational modifications of flanking regions modulate binding untested
  13. 1996 High

    Biphasic glutamate-dependent phosphoregulation was mapped: metabotropic receptors activate CaMKII/PKC to transiently phosphorylate MAP2, while NMDA receptors activate calcineurin for sustained dephosphorylation, establishing a synaptic activity-dependent phosphorylation code that switches MAP2 between microtubule and actin association.

    Evidence 32P-labeling in neurons; pharmacological dissection with receptor agonists/antagonists and kinase/phosphatase inhibitors

    PMID:8789950

    Open questions at the time
    • Specific phosphosites responsible for the actin switch not identified
    • Whether the biphasic response occurs at individual synapses unknown
  14. 1997 High

    Distinct kinase-specific functional consequences were resolved: cdc2 phosphorylation abolishes both stabilizing and nucleating activities, while PKA phosphorylation selectively eliminates nucleation without affecting stabilization, demonstrating that different phosphorylation patterns produce distinct functional outcomes.

    Evidence In vitro phosphorylation by purified PKA and cdc2; dark-field single-microtubule visualization

    PMID:9376363

    Open questions at the time
    • In vivo relevance of cdc2-mediated MAP2 regulation in postmitotic neurons unclear
    • Combinatorial effects of multiple kinases untested
  15. 1999 High

    Identification of MAP2B as an AKAP that directly binds L-type Ca²⁺ channel α1 subunits and recruits PKA to postsynaptic sites revealed a scaffolding function independent of microtubule binding, expanding MAP2's role to signaling complex assembly.

    Evidence Reciprocal Co-IP from brain; direct protein overlay binding; nocodazole control for microtubule independence

    PMID:10514522

    Open questions at the time
    • Whether channel-MAP2-PKA complex formation is activity-regulated unknown
    • Stoichiometry of the complex not determined
  16. 1999 High

    MARK kinases were identified as physiological kinases that phosphorylate KXGS motifs in the microtubule-binding domain, causing MAP2 detachment and microtubule destabilization in cells.

    Evidence Inducible MARK1/MARK2 expression in CHO cells; microtubule stability and immunofluorescence assays

    PMID:10542369

    Open questions at the time
    • MARK regulation in neurons not addressed
    • Whether MARK acts on MAP2 at synapses unknown
  17. 1999 High

    A 640-nt cis-acting dendritic targeting element in the 3′ UTR was shown to be necessary and sufficient for MAP2 mRNA dendritic localization, resolving the long-standing question of what directs MAP2 mRNA to dendrites.

    Evidence Chimeric mRNA reporters in hippocampal and sympathetic neurons; in situ hybridization

    PMID:10516301

    Open questions at the time
    • Trans-acting factors recognizing the DTE not identified
    • Whether the DTE is activity-regulated unknown
  18. 2000 High

    Phosphomimetic mutations at KXGS motifs demonstrated that phosphorylation actively redirects MAP2 from microtubules to actin-rich membrane ruffles, establishing the molecular basis for phosphorylation-dependent cytoskeletal switching.

    Evidence Site-directed KXGS-to-Glu mutagenesis in HeLa cells; immunofluorescence; biochemical fractionation

    PMID:11029056

    Open questions at the time
    • Whether this switch occurs dynamically at synapses in neurons not shown
    • Actin-binding surface versus microtubule-binding surface overlap not structurally resolved
  19. 2002 High

    MAP2 knockout mice revealed essential roles in dendritic elongation, microtubule density maintenance, and PKA/CREB signaling in dendrites, establishing MAP2 as both a structural and signaling scaffold in vivo.

    Evidence MAP2-deficient mice; microtubule density measurement; PKA subunit and phospho-CREB assays in cultured neurons

    PMID:12163474

    Open questions at the time
    • Behavioral consequences of full MAP2 knockout not reported in this study
    • Compensatory changes by tau or MAP1B not assessed
  20. 2003 High

    Targeted deletion of the N-terminal PKA-anchoring domain showed that MAP2's AKAP function is specifically required for contextual fear memory, dissociating the signaling role from microtubule stabilization in a behavioral paradigm.

    Evidence N-terminal deletion mice by homologous recombination; fear conditioning behavioral tests; phosphorylation analysis

    PMID:12763072

    Open questions at the time
    • Downstream PKA substrates mediating contextual memory not identified
    • Whether other AKAPs compensate partially unknown
  21. 2003 Medium

    Quantitative binding of the neurosteroid DHEA to the MAP2c N-terminus (Ka ~2.7×10⁷ M⁻¹) identified MAP2 as a direct neurosteroid receptor, a function previously unrecognized for a cytoskeletal protein.

    Evidence Isothermal titration calorimetry; tryptic digestion and mass spectrometry domain mapping

    PMID:12775713

    Open questions at the time
    • In vivo relevance of neurosteroid–MAP2 interaction not demonstrated in this study
    • Whether DHEA binding alters MAP2 microtubule affinity untested
  22. 2006 Medium

    RNAi knockdown confirmed MAP2 is required for pregnenolone-stimulated neurite extension, validating MAP2 as a functional neurosteroid receptor that couples steroid binding to microtubule polymerization and neurite growth.

    Evidence MAP2 RNAi in PC12 cells; neurite outgrowth with PREG/MePREG; nocodazole protection assay

    PMID:16537405

    Open questions at the time
    • Binding site for PREG on MAP2 not mapped at residue resolution
    • Whether neurosteroid regulation of MAP2 occurs in vivo in adult brain unknown
  23. 2011 Medium

    Single-molecule RNA imaging revealed MAP2 mRNA travels in small ribonucleoprotein particles whose composition is regulated by synaptic activity and Staufen 2, linking activity-dependent translational control to MAP2 mRNA transport.

    Evidence Single-molecule FISH; Staufen 2 manipulation; synaptic activity modulation

    PMID:21869818

    Open questions at the time
    • Whether Staufen 2 directly binds the MAP2 3′ UTR DTE not shown
    • Translational output from individual RNPs not measured
  24. 2019 Medium

    NMR and cryo-EM structural analysis established that MAP2c is intrinsically disordered in solution but adopts defined conformations upon microtubule and F-actin binding, with transient local structural motifs (molecular recognition elements) marking functional interaction sites.

    Evidence NMR conformational analysis; cryo-EM; comparison of free versus complex-bound states

    PMID:30884818

    Open questions at the time
    • High-resolution structure of MAP2 bound to microtubules not achieved
    • How phosphorylation alters these transient structures at atomic resolution unresolved
  25. 2023 Medium

    Biophysical measurements revealed MAP2 makes microtubules more flexible than tau does, correlating with increased process branching in neuronal cells, providing a mechanical basis for MAP2's role in dendritic (branched) versus tau's role in axonal (linear) architecture.

    Evidence Fluorescence microscopy of microtubules in hydrodynamic flow; teardrop flexural rigidity analysis; SH-SY5Y transfection

    PMID:37258650

    Open questions at the time
    • Whether flexibility differences arise from distinct binding geometries or stoichiometries not resolved
    • In vivo measurement of microtubule flexural rigidity in dendrites versus axons not performed

Open questions

Synthesis pass · forward-looking unresolved questions
  • A high-resolution structural model of full-length MAP2 bound to microtubules is lacking, and how the multiple regulatory phosphorylation inputs are integrated at individual synapses to dynamically control MAP2 cytoskeletal switching, AKAP scaffolding, and neurosteroid reception remains an open question.
  • No atomic-resolution structure of MAP2–microtubule complex
  • Combinatorial phosphorylation code not decoded in vivo
  • Compensation between MAP2, tau, and MAP1B in dendritic function not systematically addressed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 9 GO:0005198 structural molecule activity 5 GO:0060090 molecular adaptor activity 3 GO:0008289 lipid binding 1
Localization
GO:0005856 cytoskeleton 10 GO:0005829 cytosol 3
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1852241 Organelle biogenesis and maintenance 4 R-HSA-112316 Neuronal System 3

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1988 The carboxyl-terminal domain of MAP2 containing three imperfect 18-amino acid repeats constitutes the microtubule binding site. A subcloned fragment spanning the first two repeats co-purified with microtubules through successive polymerization/depolymerization cycles, whereas the amino-terminal region failed to co-purify. In vitro translation of subcloned MAP2 fragments followed by microtubule co-purification (cycles of polymerization/depolymerization); complete cDNA sequencing Science High 3142041
1988 MAP2 mRNA is selectively localized in dendrites of developing brain neurons, whereas tubulin mRNA is restricted to neuronal cell bodies, demonstrating that dendritic targeting of MAP2 protein can occur via local dendritic mRNA translation. In situ hybridization with specific cDNA probes on developing brain tissue Nature High 3200318
1984 MAP2 is selectively localized to neuronal dendrites and dendritic spines (including postsynaptic densities), but is absent from axons, as demonstrated with monoclonal antibodies. MAP2 association with postsynaptic densities and spines suggests functions independent of microtubule binding. Immunocytochemistry with monoclonal hybridoma antibodies on brain tissue sections; immunoelectron microscopy The Journal of neuroscience High 6699682
1988 MAP2 forms crossbridges between microtubules and neurofilaments in neuronal dendrites in vivo. Reconstitution experiments showed MAP2 binds neurofilament L protein in vitro and crosslinks neurofilaments with microtubules. Quick-freeze deep-etch immunoelectron microscopy with anti-MAP2 antibody and ferritin-labeled secondary; in vitro reconstitution with isolated neurofilament L protein and MAP2 The Journal of neuroscience High 3045269
1992 MAP2 expression in non-neuronal fibroblasts via cDNA transfection stabilizes microtubules against depolymerizing reagents and promotes accumulation of acetylated alpha-tubulin, demonstrating that MAP2 directly confers microtubule stability in living cells. cDNA transfection of MAP2/MAP2c into fibroblasts; treatment with microtubule depolymerizing reagents; immunofluorescence for acetylated tubulin Journal of cell science High 1487506
2002 MAP2 is required for dendritic elongation and serves as an anchoring protein for the regulatory subunit II of cAMP-dependent protein kinase (PKA) in dendrites. MAP2-knockout mice show reduced microtubule density and dendritic length, reduced PKA subunits in dendrites, and impaired CREB phosphorylation after forskolin stimulation. MAP2-deficient (knockout) mice; microtubule density measurement; PKA subunit immunostaining and Western blot; phospho-CREB assay after forskolin stimulation in cultured neurons The Journal of cell biology High 12163474
1990 NMDA receptor activation induces rapid dephosphorylation (~70% decrease) of MAP2 in hippocampal slices without changing total MAP2 levels. The effect is blocked by NMDA antagonists and is distinct from non-NMDA receptor activation, suggesting calcium/calmodulin-dependent phosphatase (calcineurin) mediates NMDA-induced MAP2 dephosphorylation. 32P-orthophosphate labeling of hippocampal slices; pharmacological dissection with competitive and non-competitive NMDA antagonists; SDS-PAGE phosphoprotein analysis Neuron High 2169265
1984 Pre-phosphorylation of MAP2 by a co-purifying cAMP-independent protein kinase decreases MAP2 affinity for taxol-stabilized microtubules and increases the dissociation rate of microtubule polymerization in a phosphorylation level-dependent manner, demonstrating that MAP2 phosphorylation regulates microtubule binding and length. In vitro kinase phosphorylation of MAP2; microtubule binding assays with taxol-stabilized microtubules; polymerization kinetics measurements European journal of biochemistry High 6146522
1996 Glutamate produces a biphasic regulation of MAP2 phosphorylation: rapid transient increase via metabotropic receptors (attenuated by CaMKII and PKC inhibitors), followed by persistent dephosphorylation via NMDA receptors and calcineurin (calcium/calmodulin-dependent phosphatase 2B). MAP2 phosphorylation state determines its interaction with microtubules and actin. 32P-labeling of neurons; pharmacological dissection with glutamate receptor agonists/antagonists, CaMKII inhibitors, PKC inhibitors, calcineurin inhibitors; immunoprecipitation Neuron High 8789950
1990 The repeated tubulin-binding sequence motif in both MAP2 and tau also mediates actin binding. A synthetic peptide corresponding to one of the repeated tubulin-binding sites binds G-actin by affinity chromatography and co-sediments with F-actin. Affinity chromatography of G-actin on synthetic peptide column; co-sedimentation of F-actin with peptide; immunoelectron microscopy co-localization The Biochemical journal High 2115775
1999 MAP2B (a high molecular weight MAP2 isoform) directly binds the alpha1 subunit of class C L-type Ca2+ channels and serves as an A-kinase anchor protein (AKAP) that recruits PKA to postsynaptic sites containing these channels. MAP2B association with channels is microtubule-independent. Immunoprecipitation from rat brain extracts; direct protein overlay binding assay with 32P-labeled RIIβ; immunoblotting; in vitro binding assay with purified channel alpha1 subunit; nocodazole treatment to rule out microtubule dependence The Journal of biological chemistry High 10514522
1999 MARK kinases phosphorylate MAP2c (and MAP4) on their microtubule-binding domain in transfected CHO cells, causing detachment of MAP2 from microtubules, increased microtubule dynamic instability, and eventual microtubule disruption and vimentin network breakdown. Inducible expression of MARK1/MARK2 in CHO cells; immunofluorescence; microtubule stability assays; phosphorylation-state analysis Cell motility and the cytoskeleton High 10542369
1989 High molecular weight MAP2 isoforms (MAP2a/b) contain a large N-terminal sidearm domain responsible for cross-linking dendritic microtubules and a dendritic targeting signal. The embryonic MAP2c isoform, generated by alternative splicing lacking 1,342 amino acids of the sidearm, has no dendritic mRNA targeting, indicating the targeting signal is specific to the high-molecular-weight forms. cDNA cloning and sequencing of MAP2 isoforms; in situ hybridization for MAP2c mRNA; electron microscopy of reconstituted microtubules Nature High 2770869
1993 MAP2c-stabilized microtubule bundles in transfected non-neuronal cells support process outgrowth when actin is depolymerized by cytochalasin B. This effect is specific to MAP2c and does not occur with taxol-stabilized microtubules, demonstrating that MAP2c confers stability, bundling, and stiffness to microtubules—properties required for neurite-like process formation. MAP2c cDNA transfection into non-neuronal cells; cytochalasin B treatment; video time-lapse microscopy; comparison with taxol-treated controls Development High 8392463
2000 cAMP-dependent protein kinase (PKA) activity disrupts the MAP2c-microtubule interaction in HeLa cells by phosphorylating serines within KXGS motifs (one per tubulin-binding repeat). Double or triple KXGS-to-glutamate mutations promote MAP2c redistribution to peripheral actin-enriched membrane ruffles, demonstrating phosphorylation-dependent switching between microtubule and actin cytoskeletal associations. PKA activation in HeLa cells expressing MAP2c; site-directed mutagenesis of KXGS motifs to glutamate (phosphomimetic); immunofluorescence and detergent extraction to assess cytoskeletal association; biochemical fractionation Molecular biology of the cell High 11029056
1999 A 640-nucleotide cis-acting dendritic targeting element (DTE) within the 3' UTR of MAP2 mRNA is both necessary and sufficient for dendritic localization of chimeric mRNAs in hippocampal and sympathetic neurons. The 5' UTR and coding region do not confer dendritic targeting. Chimeric mRNA reporter constructs transfected into hippocampal neurons and microinjected into sympathetic neurons; in situ hybridization to detect RNA distribution The Journal of neuroscience High 10516301
1997 Phosphorylation of MAP2 by cdc2 kinase (7-10 mol phosphate/mol MAP2, >60% in microtubule-binding region) abolishes both microtubule-stabilizing and microtubule-nucleating activities. PKA phosphorylation (15 mol/mol, ~70% in projection region) reduces only microtubule-nucleating activity, not stabilizing activity. Direct observation of individual microtubules by dark-field microscopy revealed distinct mechanistic consequences. In vitro phosphorylation by purified PKA and cdc2 kinase; dark-field microscopy of individual microtubules; quantification of polymerization phases and nucleation Biochemistry High 9376363
2000 GSK3β phosphorylates MAP2c at Thr1620/Thr1623 (recognized by antibody 305) in co-transfected COS-1 cells, preventing microtubule bundle formation. Lithium chloride (GSK3 inhibitor) reverses this effect. Highly phosphorylated MAP2c species are enriched in cytoskeleton-unbound fractions. Co-transfection of MAP2c with wild-type or mutant GSK3β in COS-1 cells; lithium chloride inhibitor treatment; immunofluorescence for microtubule bundles; cytoskeletal fractionation; site-specific antibody staining European journal of cell biology High 10826493
1992 MAP2c reorganizes cellular microtubules into stable bundles independent of the microtubule-organizing center (MTOC) when expressed in non-neuronal cells. The bundles are stiff and long, with curvature only from cortical cytoskeleton constraint, demonstrating MAP2c imparts both stability and stiffness to microtubules. cDNA transfection of MAP2c into non-neuronal cell lines; immunofluorescence; comparison with taxol and DMSO treatment Development High 1338311
1989 Biotin-labeled MAP2 microinjected into spinal cord neurons enters both axons and dendrites initially, but is selectively lost from axons over 3+ days. Immunoelectron microscopy shows axonal MAP2 is largely not cytoskeleton-associated, whereas dendritic MAP2 is cytoskeleton-bound, indicating differential cytoskeletal affinity (not sorting at cell body) underlies MAP2 compartmentalization. Microinjection of biotin-labeled MAP2 into cultured spinal cord neurons; immunoelectron microscopy; detergent extraction prior to immunocytochemistry Proceedings of the National Academy of Sciences of the United States of America High 2657741
1993 MAP2C stabilizes microtubule bundles such that <10% of tubulin is exchanged within 1 hour (assessed by photoactivation of caged fluorescein-tubulin), yet exogenously introduced tubulin rapidly incorporates at distal bundle ends. This reveals that MAP2c-bundled microtubules are extremely stable internally while remaining capable of assembly at ends. Photoactivation of caged fluorescein-labeled tubulin in MAP2c-transfected fibroblasts; microinjection of biotin-labeled tubulin; immunofluorescence with anti-biotin The Journal of cell biology High 8421058
2006 The neurosteroid pregnenolone (PREG) and its analog MePREG bind directly to MAP2 and stimulate microtubule polymerization. RNAi knockdown of MAP2 abolishes the stimulatory effects of PREG/MePREG on neurite extension in NGF-treated PC12 cells but does not affect progesterone action, demonstrating MAP2 is the specific receptor for these neurosteroids. Neurite outgrowth assays in PC12 cells; RNA interference knockdown of MAP2; nocodazole protection assay; MAP2 immunostaining quantification Proceedings of the National Academy of Sciences of the United States of America Medium 16537405
2003 DHEA binds specifically to the N-terminal region of MAP2c with an association constant of 2.7×10^7 M^-1 at 1:1 molar ratio, as measured by isothermal titration calorimetry. Tryptic digestion and mass spectrometry localized the binding site to the N-terminus. Structural modeling based on sequence homology with 17β-hydroxysteroid dehydrogenase 1 identified specific hydrogen bonds orienting DHEA in the binding pocket. Isothermal titration calorimetry; partial tryptic digestion; mass spectrometry; computational structural modeling The Journal of biological chemistry Medium 12775713
1994 ApoE3 but not ApoE4 binds MAP2c with high avidity (detectable down to 10^-9 M MAP2c and 10^-8 M apoE3), paralleling its differential binding to tau. This isoform-specific interaction suggests apoE genotype may affect intracellular microtubule maintenance via MAP2c binding. Direct binding assay between apoE isoforms and MAP2c; concentration-dependent binding analysis Neuroscience letters Medium 7891887
1994 MAP2 microtubule binding requires the repeat domain plus contiguous sequences on either side (particularly the proline-rich domain N-terminal to the repeats). Deletion mutant analysis shows binding strength increases with number of repeats present, and microtubule bundling and process outgrowth capacity correlate with binding strength. Series of deletion mutants of MAP2c transfected into non-neuronal cells; immunofluorescence for microtubule association and bundle formation; process outgrowth assay Journal of cell science High 7699010
1994 High-molecular-weight MAP2 binds phosphatidylinositol with high affinity (Kd ~51 nM) compared to MAP2c, tau, and recombinant human tau (~1.4-2.4 μM). The high affinity is due to two interactions: a low-affinity site in the C-terminal domain shared with MAP2c/tau, and a high-affinity site (Kd ~221 nM) in the MAP2-specific projection domain eliminated by alternative splicing in MAP2c. Binding to phosphatidylinositol and phosphatidylcholine vesicles; thrombin digestion of MAP2c; affinity measurements Biochemistry Medium 8025110
1996 Juvenile MAP2c and mature (full-length) MAP2 induce distinct patterns of process outgrowth in Sf9 insect cells: MAP2c induces multiple short thin processes with closely-spaced microtubules, while mature MAP2 induces single thick processes with proximo-distal taper and decreasing microtubule number, establishing MAP2 isoforms as architectural determinants of process morphology. Baculovirus expression in Sf9 cells; electron microscopy of processes; measurement of microtubule spacing and number along processes Molecular biology of the cell Medium 8868472
1992 MAP2 forms antiparallel dimers as shown by electron microscopy and antibody labeling. Intact MAP2 forms rod-like particles of ~97 nm. Major chymotryptic fragments map to a 36 kDa microtubule-binding fragment (~49 nm rods) and the AP18 antibody epitope maps to the first 151 residues; AP18 binding is phosphorylation-dependent. Limited proteolysis; electron microscopy; antibody epitope mapping; phosphorylation-dependent antibody binding assay Journal of structural biology Medium 1373291
1997 MAP2 phosphorylation at Ser136 (a Ser-Pro motif) in vivo and in vitro is catalyzed by proline-directed kinases (MAP kinase, GSK-3, cdk family members) but not by PKA, PKC, or CaMKII. This site is endogenously phosphorylated in brain MAP2. Microinjection of MAP2 into cells induces microtubule reorganization regardless of Ser136 phosphorylation state. Site-directed mutagenesis of Ser136; in vitro phosphorylation with multiple purified kinases; monoclonal antibody AP18 for phospho-specific detection; microinjection into cell lines European journal of cell biology High 7525290
1983 MAP2 binds to a poly(dA)4/poly(dT)4 sequence present in mouse satellite DNA (Sau96.1 restriction fragment). DNase protection assay showed MAP2 specifically protects this dA/dT sequence from digestion. Affinity binding of MAP2 to satellite DNA restriction fragments; DNase I protection assay The EMBO journal Low 10872313
2011 MAP2 mRNA localizes to dendrites in distinct ribonucleoprotein particles (RNPs) containing very few RNA molecules per particle. The number of MAP2 mRNA molecules per RNP is regulated by synaptic activity and by Staufen 2, demonstrating that RNP composition controlling MAP2 mRNA transport is dynamically controlled. Single-molecule fluorescence in situ hybridization; Staufen 2 manipulation; synaptic activity modulation; quantitative RNP analysis EMBO reports Medium 21869818
2012 L1CAM (L1 cell adhesion molecule) binds directly to MAP2c via ELISA, and promotes MAP2a/b/c expression through the MAPK pathway. L1-deficient mice show reduced MAP2c mRNA and protein. Co-immunoprecipitation shows MAP2a/b associates with L1 via intermediate partners. Combined L1 and MAP2 deficiency reduces neurite outgrowth. ELISA direct binding assay (MAP2c to intracellular domain of L1); co-immunoprecipitation; L1-deficient mouse brain analysis; MAPK pathway inhibition; neurite outgrowth assays Molecular and cellular neurosciences Medium 22503709
1995 A MAP2-associated kinase (embryonic MAP2 kinase, Mr=100,000) co-purified with chicken embryonic MAP2 reverses MAP2-mediated inhibition of microtubule-based motor (kinesin/dynein) motility by phosphorylating MAP2 at serine residues and releasing it from microtubules. This kinase is cAMP-independent and distinct from cdc2, MAPK, bovine MAP2 kinase, and NIMA kinase. In vitro microtubule gliding motility assay; kinase co-purification; phosphorylation analysis; inhibitor profiling The Journal of biological chemistry Medium 7759496
2003 Deletion of the N-terminal 158 amino acids of MAP2 (which contains the PKA-RIIβ binding site) in mice results in decreased MAP2 phosphorylation efficiency, major changes in hippocampal neuron morphology, and selective impairment of contextual (but not auditory cue) fear memory, demonstrating that PKA anchoring to MAP2 is essential for contextual memory formation. Homologous recombination gene targeting (N-terminal deletion); immunohistochemistry; behavioral fear conditioning tests; biochemical phosphorylation analysis Neuroscience High 12763072
2019 NMR and cryo-EM analysis reveals that MAP2c and tau40 are intrinsically disordered but contain transient local structural motifs (molecular recognition elements) in free solution. These short sequence motifs exhibiting transient structure correspond to functional interaction sites, and their interactions are regulated by phosphorylation. MAP2c and tau40 adopt defined conformations when bound to microtubules and filamentous actin. Nuclear magnetic resonance (NMR) conformational analysis; cryo-electron microscopy; comparison of free vs. complex-bound conformations; phosphorylation state analysis Biomolecules Medium 30884818
2023 MAP2 microtubule-binding domain fragments make microtubules more flexible (less straight) compared to tau-bound microtubules, as measured by teardrop pattern analysis in hydrodynamic flow. In SH-SY5Y cells, processes expressing MAP2 show more branching than tau-expressing processes. MAP2 differs from tau in imparting lower flexural rigidity to microtubules. Fluorescence microscopy of microtubules in hydrodynamic flow; teardrop pattern flexural rigidity analysis; transfection of MAP2/tau/MAP4 in SH-SY5Y cells; electron microscopy of processes Scientific reports Medium 37258650
2020 NCAM2 forms a protein complex with MAP2 and 14-3-3γ/ζ in neurons. NCAM2 depletion leads to destabilization of the microtubular network and reduced MAP2 signal, severe dendritic architecture defects, and impaired neuronal polarization both in vitro and in vivo. Proteomic analysis; co-immunoprecipitation; NCAM2 shRNA knockdown in hippocampal neurons; in utero electroporation for in vivo studies; immunofluorescence Cerebral cortex Medium 32043120
2006 TTLL7, a beta-tubulin polyglutamylase, is required for growth of MAP2-positive neurites. TTLL7 accumulates in the MAP2-enriched somatodendritic compartment, and RNAi knockdown of TTLL7 represses NGF-stimulated MAP2-positive neurite growth in PC12 cells while reducing polyglutamylated beta-tubulin. In vitro polyglutamylation assay with recombinant TTLL7; siRNA knockdown in PC12 and superior cervical ganglion neurons; immunofluorescence; Western blot The Journal of biological chemistry Medium 16901895

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
1997 A second serine protease associated with mannan-binding lectin that activates complement. Nature 667 9087411
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2008 Large-scale proteomics and phosphoproteomics of urinary exosomes. Journal of the American Society of Nephrology : JASN 607 19056867
1988 Selective localization of messenger RNA for cytoskeletal protein MAP2 in dendrites. Nature 499 3200318
1988 Microtubule-associated protein MAP2 shares a microtubule binding motif with tau protein. Science (New York, N.Y.) 463 3142041
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2021 The Cytoskeletal Elements MAP2 and NF-L Show Substantial Alterations in Different Stroke Models While Elevated Serum Levels Highlight Especially MAP2 as a Sensitive Biomarker in Stroke Patients. Molecular neurobiology 26 33931805