PMID- 21385839
OWN - NLM
STAT- MEDLINE
DCOM- 20110719
LR  - 20211203
IS  - 1477-9137 (Electronic)
IS  - 0021-9533 (Print)
IS  - 0021-9533 (Linking)
VI  - 124
IP  - Pt 7
DP  - 2011 Apr 1
TI  - Phosphorylation of kinesin light chain 1 at serine 460 modulates binding and 
      trafficking of calsyntenin-1.
PG  - 1032-42
LID - 10.1242/jcs.075168 [doi]
AB  - 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.
FAU - Vagnoni, Alessio
AU  - Vagnoni A
AD  - MRC Centre for Neurodegeneration Research, Institute of Psychiatry, King's 
      College London, PO Box 37, De Crespigny Park, Denmark Hill, London SE5 8AF, UK.
FAU - Rodriguez, Lilia
AU  - Rodriguez L
FAU - Manser, Catherine
AU  - Manser C
FAU - De Vos, Kurt J
AU  - De Vos KJ
FAU - Miller, Christopher C J
AU  - Miller CC
LA  - eng
GR  - G0501573/MRC_/Medical Research Council/United Kingdom
GR  - WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110308
PL  - England
TA  - J Cell Sci
JT  - Journal of cell science
JID - 0052457
RN  - 0 (CLSTN1 protein, human)
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (Clstn1 protein, mouse)
RN  - 0 (KLC1 protein, human)
RN  - 0 (Kns2 protein, mouse)
RN  - 0 (Microtubule-Associated Proteins)
RN  - EC 3.6.4.4 (Kinesins)
SB  - IM
MH  - Amino Acid Motifs
MH  - Amino Acid Substitution
MH  - Animals
MH  - CHO Cells
MH  - Calcium-Binding Proteins/genetics/*metabolism
MH  - Cell Line
MH  - Cricetinae
MH  - Cricetulus
MH  - Humans
MH  - Kinesins
MH  - Microtubule-Associated Proteins/*chemistry/genetics/*metabolism
MH  - Phosphorylation
MH  - Protein Binding
MH  - Protein Transport
PMC - PMC3056604
EDAT- 2011/03/10 06:00
MHDA- 2011/07/20 06:00
PMCR- 2011/10/01
CRDT- 2011/03/10 06:00
PHST- 2011/03/10 06:00 [entrez]
PHST- 2011/03/10 06:00 [pubmed]
PHST- 2011/07/20 06:00 [medline]
PHST- 2011/10/01 00:00 [pmc-release]
AID - jcs.075168 [pii]
AID - 10.1242/jcs.075168 [doi]
PST - ppublish
SO  - J Cell Sci. 2011 Apr 1;124(Pt 7):1032-42. doi: 10.1242/jcs.075168. Epub 2011 Mar 
      8.