| 2001 |
SYTL3 (Slp3) was identified as a novel C-terminal-type tandem C2 protein (synaptotagmin-like protein family). Subcellular fractionation showed it is a peripheral membrane protein. The C2A domain of Slp3 showed Ca2+-dependent phospholipid binding activity, making it a Ca2+-dependent isoform unlike Slp1 and Slp2. The C-terminus of Slp3 bound neurexin Iα in vitro. |
Subcellular fractionation, phospholipid binding experiments, in vitro binding assay |
Biochemical and biophysical research communications |
Medium |
11243866
|
| 2001 |
Sequence alignment of Slp3-a with other Slp family members revealed two conserved N-terminal regions (SHD1 and SHD2, Slp homology domains) which may function as protein interaction sites. The SHD1 and SHD2 of Slp3-a are separated by a putative Zn2+-binding sequence. Two alternative splicing isoforms of Slp3 were identified: Slp3-a and Slp3-b, sharing the same C-terminal tandem C2 structures but differing in N-terminal sequences. |
Molecular cloning, sequence alignment, RT-PCR tissue distribution analysis |
Biochemical and biophysical research communications |
Low |
11327731
|
| 2002 |
The C2A domain of Slp3 exhibits Ca2+-dependent phospholipid-binding activity. Unlike other C-type tandem C2 proteins requiring five conserved acidic residues in Ca2+-binding loops, the Slp3 C2A domain contains only one conserved acidic residue in loop 1. Site-directed mutagenesis identified Glu-336, Glu-337 in Ca2+-binding loop 1 and a polybasic sequence (Lys-359, Lys-360, Lys-361) in the β-4 strand as crucial for Ca2+-dependent phospholipid binding, unlike the analogous region in synaptotagmin I C2A which is dispensable. |
In vitro Ca2+-dependent phospholipid binding assay, site-directed mutagenesis, chimeric domain analysis |
The Biochemical journal |
High |
12049610
|
| 2002 |
Expression of Slp3-a (which contains the N-terminal Rab27A-binding SHD domain), but not Slp3-b (lacking this domain), promotes neuropeptide Y (NPY) secretion in PC12 cells, indicating that Slp3-a controls regulated dense-core vesicle exocytosis via binding to Rab27A. This is in contrast to Slp4-a/granuphilin-a, which inhibits secretion. |
Overexpression in PC12 cells, NPY secretion assay, immunocytochemistry, subcellular fractionation |
The Journal of biological chemistry |
Medium |
12176990
|
| 2001 |
Melanophilin (Mlph/leaden), a protein with homology to Rab effectors including Slp3-a, was identified as a critical component of the melanosome transport machinery, supporting the model that Slp3-a family members function as Rab effectors in vesicle transport. Mlph possesses two Zn2+-binding CX2CX13,14CX2C motifs and an aromatic-rich region critical for Rab binding, but unlike Slp3-a, lacks two Ca2+-binding C2 domains. |
Genetic mapping of leaden locus, sequence homology analysis, functional complementation studies in mice |
Proceedings of the National Academy of Sciences of the United States of America |
Low |
11504925
|
| 2012 |
Slp3 (SYTL3) functions as a Rab27a effector in cytotoxic T lymphocytes (CTLs) and interacts with kinesin-1 through the tetratricopeptide repeat (TPR) domain of kinesin-1 light chain. The Rab27a/Slp3/kinesin-1 transport complex mediates terminal transport and secretion of lytic granules to the immune synapse. Inhibition of this complex impairs lytic granule secretion. |
Co-immunoprecipitation, knockdown/inhibition studies, live-cell imaging, CTL killing assays |
Blood |
High |
22308290
|
| 2015 |
Increasing expression of Slp3 in Chediak-Higashi syndrome (LYST-deficient) CTLs restored the dynamics and secretory ability of cytotoxic granules at the immunological synapse, placing Slp3 downstream of LYST in the lytic granule exocytosis pathway. |
Overexpression rescue in patient-derived CHS CTLs, confocal microscopy, correlative light-electron microscopy |
Traffic (Copenhagen, Denmark) |
Medium |
25425525
|
| 2015 |
Slp3 (SYTL3) is required for Rab27a-dependent association of HIV-1 Pr55(Gag) with the plasma membrane of CD4+ T cells. Screening of Rab27a effectors identified Slp2a, Slp3, and Slac2b as required for Pr55(Gag) membrane association, linking SYTL3 to HIV-1 assembly downstream of Rab27a. |
RNAi knockdown, confocal microscopy, Pr55(Gag) membrane association assay in CD4+ T cells |
The Journal of cell biology |
Medium |
25940347
|
| 2016 |
In mast cells, Slp3 is the critical effector linking kinesin-1 to Rab27b-associated secretory granules. Kinesin-1 recruitment to the Slp3/Rab27b effector complex is independent of microtubule reorganization but requires PI3K activity upon IgE receptor stimulation. The PI3K-dependent formation of the kinesin-1/Slp3/Rab27b complex is critical for microtubule-dependent secretory granule movement required for mast cell degranulation and IgE-mediated anaphylaxis in vivo. |
Kif5b conditional knockout mice, bone marrow-derived mast cell degranulation assays, passive systemic anaphylaxis model, co-immunoprecipitation, pharmacological PI3K inhibition |
The Journal of cell biology |
High |
27810912
|
| 2008 |
Slp3 (Slp1/Slp2-a) proteins localize predominantly to the plasma membrane of both human and mouse CTLs. In CTLs, Slp3-a expression was not detected (only Slp1 and Slp2-a were found), indicating cell-type-specific expression of Slp family members. |
RT-PCR screening, immunofluorescence/confocal microscopy, flow cytometry in human and mouse CTLs |
Traffic (Copenhagen, Denmark) |
Low |
18266782
|
| 2020 |
Knockdown of SYTL3 (or Rab27b) in bladder cancer cells increased intracellular BCG quantity and cytotoxicity, while overexpression of Rab27b reduced them. This indicates that SYTL3 functions as an effector of Rab27b to mediate exocytosis of BCG from urothelial cells, contributing to BCG therapy resistance. |
shRNA knockdown, overexpression, mouse orthotopic xenograft model, intracellular BCG quantification |
Molecular cancer therapeutics |
Medium |
32737155
|
| 2021 |
SYTL3 knockout in human neurons (hESC-derived) or knockdown of Sytl3 in embryonic mouse cortex markedly promotes neuronal migration. SYTL3-KO caused abnormal distribution of deep-layer neurons in brain organoids and reduced presynaptic neurotransmitter release. SYTL3-KO-accelerated neuronal migration is modulated by high expression of matrix metalloproteinases. |
CRISPR knockout in hESC-derived neurons, in utero shRNA knockdown in mouse cortex, brain organoids, MMP inhibitor experiments, neurotransmitter release assay |
Cell reports |
Medium |
33657377
|
| 2022 |
In mast cells, Slp3 (a cargo adaptor) recruitment to secretory granules was independent of kinesin-1 motor association: kinesore treatment (which activates kinesin-1) had no effect on Slp3 levels in a granule-enriched biochemical fraction, even though it inhibited granule transport and exocytosis. This dissociates granule-adaptor loading from motor recruitment. |
shRNA Kif5b knockdown, live-cell imaging, biochemical granule fractionation, kinesore pharmacological treatment |
PloS one |
Medium |
35316306
|