2015年1月
LRRK1-phosphorylated CLIP-170 regulates EGFR trafficking by recruiting p150(Glued) to microtubule plus ends
JOURNAL OF CELL SCIENCE
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- 巻
- 128
- 号
- 2
- 開始ページ
- 385
- 終了ページ
- 396
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1242/jcs.161547
- 出版者・発行元
- COMPANY OF BIOLOGISTS LTD
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 C-terminal 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 p150(Glued) (also known as DCTN1) a subunit of dynactin, at microtubule plus ends, thereby facilitating the migration of EGFR-containing endosomes. Thus, our findings provide new mechanistic insights into the dynein-driven transport of EGFR.
- リンク情報
- ID情報
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- DOI : 10.1242/jcs.161547
- ISSN : 0021-9533
- eISSN : 1477-9137
- PubMed ID : 25413345
- Web of Science ID : WOS:000347973900019