Leucine-rich repeat kinase LRRK1 regulates endosomal trafficking of the EGF receptor

Hiroshi Hanafusa, Kouki Ishikawa, Shin Kedashiro, Tsukasa Saigo, Shun-ichiro Iemura, Tohru Natsume, Masayuki Komada, Hiroshi Shibuya, Atsuki Nara and Kunihiro Matsumoto ()
Additional contact information
Hiroshi Hanafusa: Graduate school of Science, Nagoya University, Chikusa-ku
Kouki Ishikawa: Graduate school of Science, Nagoya University, Chikusa-ku
Shin Kedashiro: Graduate school of Science, Nagoya University, Chikusa-ku
Tsukasa Saigo: Graduate school of Science, Nagoya University, Chikusa-ku
Shun-ichiro Iemura: National Institutes of Advanced Industrial Science and Technology, Biological Information Research Center (JBIRC), Kohtoh-ku
Tohru Natsume: National Institutes of Advanced Industrial Science and Technology, Biological Information Research Center (JBIRC), Kohtoh-ku
Masayuki Komada: Graduate school of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259-B-16 Nagatsuta, Midori-ku
Hiroshi Shibuya: Medical Research Institute, Tokyo Medical and Dental University, Chiyoda-ku
Atsuki Nara: Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology
Kunihiro Matsumoto: Graduate school of Science, Nagoya University, Chikusa-ku

Nature Communications, 2011, vol. 2, issue 1, 1-12

Abstract: Abstract Activation of the epidermal growth factor receptor (EGFR) not only initiates multiple signal-transduction pathways, including the MAP kinase (MAPK) pathway, but also triggers trafficking events that relocalize receptors from the cell surface to intracellular endocytic compartments. In this paper, we demonstrate that leucine-rich repeat kinase LRRK1, which contains a MAPKKK-like kinase domain, forms a complex with activated EGFR through an interaction with Grb2. Subsequently, LRRK1 and epidermal growth factor (EGF) are internalized and co-localized in early endosomes. LRRK1 regulates EGFR transport from early to late endosomes and regulates the motility of EGF-containing early endosomes in a manner dependent on its kinase activity. Furthermore, LRRK1 serves as a scaffold facilitating the interaction of EGFR with the endosomal sorting complex required for transport-0 complex, thus enabling efficient sorting of EGFR to the inner vesicles of multivesicular bodies. Our findings provide the first evidence that a MAPKKK-like protein regulates the endosomal trafficking of EGFR.

Date: 2011
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms1161 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:2:y:2011:i:1:d:10.1038_ncomms1161

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms1161

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().