Phosphorylation of multiple sites within an acidic region of Alcadein α is required for kinesin-1 association and Golgi exit of Alcadein α cargo

Yuriko Sobu, Keiko Furukori, Kyoko Chiba, Angus C. Nairn, Masataka Kinjo, Saori Hata, Toshiharu Suzuki

Research output: Contribution to journalArticlepeer-review

Abstract

Alcadein α (Alcα) is a major cargo of kinesin-1 that is subjected to anterograde transport in neuronal axons. Two tryptophan- and aspartic acid-containing (WD) motifs located in its cytoplasmic domain directly bind the tetratricopeptide repeat (TPR) motifs of the kinesin light chain (KLC), which activate kinesin-1 and recruit kinesin-1 to Alcα cargo. We found that phosphorylation of three serine residues in the acidic region located between the two WD motifs is required for interaction with KLC. Phosphorylation of these serine residues may alter the disordered structure of the acidic region to induce direct association with KLC. Replacement of these serines with Ala results in a mutant that is unable to bind kinesin-1, which impairs exit of Alcα cargo from the Golgi. Despite this deficiency, the compromised Alcα mutant was still transported, albeit improperly by vesicles following missorting of the Alcα mutant with amyloid β-protein precursor (APP) cargo. This suggests that APP partially compensates for defective Alcα in anterograde transport by providing an alternative cargo receptor for kinesin-1.

Original languageEnglish
Pages (from-to)3844-3856
Number of pages13
JournalMolecular biology of the cell
Volume28
Issue number26
DOIs
Publication statusPublished - 2017 Dec
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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