| 2008 |
SCYL1 binds COPI coat components (coatomer) via a C-terminal RKLD-COO⁻ sequence analogous to the KKXX-COO⁻ ER-retrieval motif, co-immunoprecipitates with βCOP from brain lysates, and localizes to the ERGIC and cis-Golgi in an Arf1-independent manner. RNAi-mediated knockdown of SCYL1 disrupts COPI-mediated retrograde trafficking of the KDEL receptor to the ER without affecting anterograde traffic. |
Mass spectrometry-based binding screen, pull-down assays, co-immunoprecipitation, RNAi knockdown with trafficking assay (KDEL receptor retrograde vs. anterograde) |
The Journal of biological chemistry |
High |
18556652
|
| 2007 |
Loss-of-function mutation in Scyl1 causes the murine mdf (muscle-deficient) neurodegenerative phenotype comprising cerebellar atrophy, Purkinje cell loss, and optic nerve atrophy. SCYL1 is enriched at CNS synapses and neuromuscular junctions. |
Genetic mapping of mdf mouse mutant, histopathology, immunolocalization |
EMBO reports |
Medium |
17571074
|
| 2010 |
SCYL1 knockdown increases Golgi surface area and volume and disrupts orderly Golgi ultrastructure (increased cisternal luminal width) without altering Golgi polarity or cisternae number. SCYL1 Golgi localization depends on the golgin p115 network. SCYL1 interacts with the cis-Golgi-associated protein 58K/FTCD. |
RNAi knockdown, fluorescence and electron microscopy, co-immunoprecipitation (SCYL1 with FTCD) |
PloS one |
Medium |
20209057
|
| 2010 |
SCYL1 is a cytoplasmic component of the nuclear tRNA export machinery. It binds tRNA saturably, associates with the nuclear pore complex through interaction with Nup98, co-purifies with exportin-t, exportin-5, RanGTPase, and eEF-1A, interacts directly with exportin-t and RanGTP (but not RanGDP) in vitro, and forms a quaternary complex with exportin-t, tRNA, and RanGTP in vitro. Overexpression of SCYL1 restores export of a nuclear export-defective tRNA mutant. |
tRNA export rescue assay in COS-7 cells, saturable tRNA binding assay, co-purification, in vitro binding assays (direct interaction with exportin-t, RanGTP), quaternary complex reconstitution |
Molecular biology of the cell |
High |
20505071
|
| 2012 |
Neural-specific (but not skeletal muscle-specific) deletion of Scyl1 causes progressive motor neuron disease with loss of lower motor neurons, axonal degeneration, and mislocalization/accumulation of TDP-43 and ubiquilin-2 into cytoplasmic inclusions within lower motor neurons, indicating SCYL1 acts cell-autonomously in neurons to maintain TDP-43 proteostasis. |
Conditional knockout mice (neural-specific and muscle-specific Cre), histopathology, immunofluorescence for TDP-43 and ubiquilin-2 localization |
The Journal of neuroscience |
High |
23175812
|
| 2014 |
SCYL1 oligomerizes through centrally located HEAT repeats, uses its C-terminal RKXX-COO⁻ motif to bind directly to the appendage domain of γ2-COP (COPG2), and through a distinct site selectively interacts with class II Arfs (notably Arf4), thereby scaffolding class II Arfs to γ2-bearing COPI subcomplexes. Disruption of this scaffolding function causes tubulation of the ERGIC and cis-Golgi. |
Co-immunoprecipitation, direct binding assays, domain mapping/mutagenesis, fluorescence microscopy of ERGIC/Golgi morphology upon loss of scaffolding |
Journal of cell science |
High |
24481816
|
| 2018 |
Loss of Scyl3 alone has no effect in mice, but combined deletion of Scyl1 and Scyl3 accelerates onset of motor neuron disease compared with Scyl1 deficiency alone. Disease onset correlated with earlier TDP-43 mislocalization in spinal motor neurons, indicating overlapping roles for SCYL1 and SCYL3 in TDP-43 proteostasis and motor neuron viability. |
Scyl1/Scyl3 double-knockout mice, behavioral assessment, histopathology, immunofluorescence for TDP-43 |
The Journal of neuroscience |
Medium |
29437892
|
| 2020 |
SCYL1 arginine methylation by PRMT1 at the γ2-COP-binding site is required for the SCYL1–γ2-COP interaction and normal Golgi morphology. PRMT1 co-localizes with SCYL1 in the Golgi fraction. Inhibition of PRMT1 or expression of arginine methylation-defective SCYL1 suppresses axon outgrowth and dendrite complexity via abnormal Golgi morphology. |
PRMT1 inhibition, co-localization by fractionation, siRNA knockdown of SCYL1 with rescue by wild-type vs. methylation-deficient mutant SCYL1, neurite outgrowth assays |
Molecular biology of the cell |
Medium |
32583741
|
| 2020 |
In C. elegans, the SCYL1 orthologue SCYL-1 physically interacts with the Slo2 potassium channel (SLO-2) in neurons and increases single-channel open probability (~50% reduction in scyl-1 knockout). Correspondingly, human SCYL1 doubles the open probability of human Slo2.2/Slack in a heterologous expression system, indicating an evolutionarily conserved role as a positive regulator of Slo2 channel activity. |
C. elegans genetics (scyl-1 knockout), single-channel patch-clamp electrophysiology, heterologous expression of human SCYL1 with Slo2.2/Slack, physical interaction assay |
eLife |
High |
32314960
|
| 2022 |
mTORC1 phosphorylates SCYL1 on Ser754 under growth conditions, maintaining SCYL1 at the Golgi. Upon mTORC1 inhibition, dephosphorylation of Ser754 causes SCYL1 displacement to endosomes, leading to Golgi enlargement, redistribution of early and late endosomes, and increased extracellular vesicle secretion. |
mTORC1 inhibitor treatment, phosphomutant SCYL1 (Ser754Ala), live cell imaging and organelle morphology quantification, nanoparticle tracking for extracellular vesicles |
Nature communications |
High |
35948564
|
| 2025 |
SCYL1-deficient fibroblasts (CALFAN patient-derived and SCYL1 knockout) accumulate procollagen type I in the ER, display ER distension, and show elevated ER stress and increased cell death, particularly at elevated temperatures mimicking febrile conditions. No procollagen-I trafficking defect was detected, suggesting the primary pathological mechanism is ER stress rather than direct trafficking impairment. |
Patient and KO fibroblasts, immunofluorescence/EM for procollagen-I and ER morphology, ER stress markers, cell viability assays at elevated temperature |
Disease models & mechanisms |
Medium |
41063534
|
| 2026 |
CTDSPL2 binds SCYL1 (demonstrated by Co-IP) and acts as a phosphatase that suppresses SCYL1 phosphorylation at Ser754. In PTX-resistant breast cancer cells, CTDSPL2 knockdown increases SCYL1 Ser754 phosphorylation; mutating Ser754 to alanine blocks this effect, linking CTDSPL2 to mTORC1-SCYL1 axis and extracellular vesicle secretion. |
Co-immunoprecipitation, CTDSPL2 knockdown, SCYL1 Ser754Ala phosphomutant, nanoparticle tracking for extracellular vesicles, in vivo tumorigenesis assay |
Cell cycle |
Medium |
42041204
|
| 2017 |
SCYL1 does not regulate REST protein levels or turnover: REST steady-state levels and degradation were identical in Scyl1+/+ vs. Scyl1−/− MEFs, CRISPR-Cas9 SCYL1 knockout HEK293T cells, and RNAi-depleted HEK293T or MDA-MB-231 cells. This is a negative result refuting a prior claim that SCYL1 mediates REST degradation. |
Scyl1−/− MEFs, CRISPR-Cas9 KO in HEK293T, RNAi in HEK293T and MDA-MB-231; western blot for REST levels and turnover |
PloS one |
Medium |
28570664
|