期刊
JOURNAL OF CELL SCIENCE
卷 124, 期 7, 页码 1032-1042出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.075168
关键词
Kinesin light chain 1; Calsyntenin-1; MAPK; ERK; Axonal transport; Alzheimer's disease
类别
资金
- UK Medical Research Council
- Wellcome Trust
- Alzheimer's Research Trust
- European Union
- Project MitoTarget [HEALTH-F2-2008-223388]
- MRC [G0501573] Funding Source: UKRI
- Alzheimers Research UK [ART-PhD2006-2] Funding Source: researchfish
- Medical Research Council [G0501573] Funding Source: researchfish
Kinesin light chain 1 (KLC1) binds to the intracellular cytoplasmic domain of the type-1 membrane-spanning protein calsyntenin-1 (also known as alcadein-alpha) to mediate transport of a subset of vesicles. Here, we identify serine 460 in KLC1 (KLC1ser460) as a phosphorylation site and show that mutation of KLC1ser460 influences the binding of KLC1 to calsyntenin-1. Mutation of KLC1ser460 to an alanine residue, to preclude phosphorylation, increased the binding of calsyntenin-1, whereas mutation to an aspartate residue, to mimic permanent phosphorylation, reduced the binding. Mutation of KLC1ser460 did not affect the interaction of KLC1 with four other known binding partners: huntingtin-associated protein 1 isoform A (HAP1A), collapsin response mediator protein-2 (CRMP2), c-Jun N-terminal kinase-interacting protein-1 (JIP1) and kinase-D-interacting substrate of 220 kDa (Kidins220). KLC1ser460 is a predicted mitogen-activated protein kinase (MAPK) target site, and we show that extracellular-signal-regulated kinase (ERK) phosphorylates this residue in vitro. We also demonstrate that inhibition of ERK promotes binding of calsyntenin-1 to KLC1. Finally, we show that expression of the KLC1ser460 mutant proteins influences calsyntenin-1 distribution and transport in cultured cells. Thus, phosphorylation of KLC1ser460 represents a mechanism for selectively regulating the binding and trafficking of calsyntenin-1.
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