LRRK1-phosphorylated CLIP-170 regulates EGFR trafficking by recruiting p150Glued to microtubule plus ends

Shin Kedashiro, Strahil Iv Pastuhov, Tomoki Nishioka, Takashi Watanabe, Kozo Kaibuchi, Kunihiro Matsumoto, Hiroshi Hanafusa

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)


The binding of ligand to epidermal growth factor receptor (EGFR) causes the receptor to become activated and stimulates the endocytosis of EGFR. Early endosomes containing activated EGFR migrate along microtubules as they mature into late endosomes. We have recently shown that LRRK1, which is related to the familial Parkinsonism gene product Park8 (also known as LRRK2), regulates this EGFR transport in a manner dependent on LRRK1 kinase activity. However, the downstream targets of LRRK1 that might modulate this transport function have not been identified. Here, we identify CLIP-170 (also known as CLIP1), a microtubule plus-end protein, as a substrate of LRRK1. LRRK1 phosphorylates CLIP-170 at Thr1384, located in its Cterminal zinc knuckle motif, and this promotes the association of CLIP-170 with dynein-dynactin complexes. We find that LRRK1-mediated phosphorylation of CLIP-170 causes the accumulation of p150Glued (also known as DCTN1) a subunit of dynactin, at microtubule plus ends, thereby facilitating the migration of EGFRcontaining endosomes. Thus, our findings provide new mechanistic insights into the dynein-driven transport of EGFR.

Original languageEnglish
Pages (from-to)385-396
Number of pages12
JournalJournal of cell science
Issue number2
Publication statusPublished - 2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cell Biology


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