Phosphorylation of kinesin light chain 1 at serine 460 modulates binding and trafficking of calsyntenin-1

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Kinesin light chain 1 (KLC1) binds to the intracellular cytoplasmic domain of the type-1 membrane-spanning protein calsyntenin-1 (also known as alcadein-α) 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.

Original languageEnglish
Pages (from-to)1032-42
Number of pages11
JournalJournal of Cell Science
Issue numberPt 7
Publication statusPublished - 1 Apr 2011


  • Amino Acid Motifs
  • Amino Acid Substitution
  • Animals
  • CHO Cells
  • Calcium-Binding Proteins/genetics
  • Cell Line
  • Cricetinae
  • Cricetulus
  • Humans
  • Kinesins
  • Microtubule-Associated Proteins/chemistry
  • Phosphorylation
  • Protein Binding
  • Protein Transport


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