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

ABSTRACT: Alcadein ? (Alc?) 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 Alc? 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 Alc? cargo from the Golgi. Despite this deficiency, the compromised Alc? mutant was still transported, albeit improperly by vesicles following missorting of the Alc? mutant with amyloid ?-protein precursor (APP) cargo. This suggests that APP partially compensates for defective Alc? in anterograde transport by providing an alternative cargo receptor for kinesin-1.

SUBMITTER: Sobu Y 

PROVIDER: S-EPMC5739299 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature