AATYK1A phosphorylation by Cdk5 regulates the recycling endosome pathway

Tetsuya Takano, Koji Tsutsumi, Taro Saito, Akiko Asada, Mineko Tomomura, Mitsunori Fukuda, Shin ichi Hisanaga

    Research output: Contribution to journalArticlepeer-review

    15 Citations (Scopus)

    Abstract

    Trafficking of recycling endosomes (REs) is regulated by the small GTPase, Rab11A; however, the regulatory mechanism remains elusive. Apoptosis-associated tyrosine kinase 1A (AATYK1A) is a Ser/Thr kinase expressed highly in brain. We have recently shown that AATYK1A localizes to Rab11A-positive RE and is phosphorylated at Ser34 by cyclin-dependent kinase 5 (Cdk5). Here, we have investigated a role of AATYK1A and its phosphorylation in recycling endosomal trafficking using Chinese hamster ovary-K1 (CHO-K1) cells. AATYK1A localizes predominantly to Rab11A-positive pericentrosomal endocytic recycling compartment (ERC). Phosphorylation at Ser34 of AATYK1A disrupts its accumulation in the pericentrosomal ERC. Consistently, phosphorylation-mimic mutant (AATYK1A-S34D) did not accumulate in the ERC and additionally attenuated ERC formation. ERC formation suppression can be reversed by constitutively active Rab11A-Q70L, suggesting a functional link between AATYK1A phosphorylation and Rab11A activity. Although no direct interaction between AATYK1A and Rab11A could be detected, the exchange of guanine nucleotides bound to Rab11A was significantly reduced in the presence of the phosphorylation-mimic AATYK1A-S34D. Together, our results reveal a regulatory role for AATYK1A in the formation of pericentrosomal ERC. They furthermore indicate that Cdk5 can disrupt ERC formation via Ser34 phosphorylation of AATYK1A. Finally, our data suggest a mechanism by which AATYK1A signaling couples Cdk5 to Rab11A activity.

    Original languageEnglish
    Pages (from-to)783-797
    Number of pages15
    JournalGenes to Cells
    Volume15
    Issue number7
    DOIs
    Publication statusPublished - 2010 Jun

    ASJC Scopus subject areas

    • Genetics
    • Cell Biology

    Fingerprint Dive into the research topics of 'AATYK1A phosphorylation by Cdk5 regulates the recycling endosome pathway'. Together they form a unique fingerprint.

    Cite this