TY - JOUR
T1 - LRRK1-mediated NDEL1 phosphorylation promotes cilia disassembly via dynein-2-driven retrograde intraflagellar transport
AU - Hanafusa, Hiroshi
AU - Kedashiro, Shin
AU - Gotoh, Mako
AU - Saitoh, Ko Hei
AU - Inaba, Hironori
AU - Nishioka, Tomoki
AU - Kaibuchi, Kozo
AU - Inagaki, Masaki
AU - Hisamoto, Naoki
AU - Matsumoto, Kunihiro
N1 - Funding Information:
We gratefully thank Dr Kazuhisa Nakayama and Dr Yohei Katoh for their helpful discussion. The cDNA clones of WDR34 and WDR60 were provided by the RIKEN BRC through the National Bio-Resource Project of the MEXT/AMED, Japan. Core facilities supported by Japan Science and Technology Agency.
Funding Information:
This research was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan and Japan Science and Technology Agency (JST) (Moonshot R&D; grant number JPMJMS2024 to H.H.). Open access funding provided by Nagoya University. Deposited in PMC for immediate release.
Publisher Copyright:
© 2022 Company of Biologists Ltd. All rights reserved.
PY - 2022/11
Y1 - 2022/11
N2 - Primary cilia are antenna-like organelles that regulate growth and development via extracellular signals. However, the molecular mechanisms underlying cilia dynamics, particularly those regulating their disassembly, are not well understood. Here, we show that leucine-rich repeat kinase 1 (LRRK1) plays a role in regulating cilia disassembly. The depletion of LRRK1 impairs primary cilia resorption following serum stimulation in cultured cells. Polo-like kinase 1 (PLK1) plays an important role in this process. During ciliary resorption, PLK1 phosphorylates LRRK1 at the primary cilia base, resulting in its activation. We identified nuclear distribution protein nudE-like 1 (NDEL1), which is known to positively regulate cilia disassembly, as a target of LRRK1 phosphorylation. Whereas LRRK1 phosphorylation of NDEL1 on Ser-155 promotes NDEL1 interaction with the intermediate chains of cytoplasmic dynein-2, it is also crucial for triggering ciliary resorption through dynein-2-driven retrograde intraflagellar transport. These findings provide evidence that a novel PLK1-LRRK1-NDEL1 pathway regulates cilia disassembly.
AB - Primary cilia are antenna-like organelles that regulate growth and development via extracellular signals. However, the molecular mechanisms underlying cilia dynamics, particularly those regulating their disassembly, are not well understood. Here, we show that leucine-rich repeat kinase 1 (LRRK1) plays a role in regulating cilia disassembly. The depletion of LRRK1 impairs primary cilia resorption following serum stimulation in cultured cells. Polo-like kinase 1 (PLK1) plays an important role in this process. During ciliary resorption, PLK1 phosphorylates LRRK1 at the primary cilia base, resulting in its activation. We identified nuclear distribution protein nudE-like 1 (NDEL1), which is known to positively regulate cilia disassembly, as a target of LRRK1 phosphorylation. Whereas LRRK1 phosphorylation of NDEL1 on Ser-155 promotes NDEL1 interaction with the intermediate chains of cytoplasmic dynein-2, it is also crucial for triggering ciliary resorption through dynein-2-driven retrograde intraflagellar transport. These findings provide evidence that a novel PLK1-LRRK1-NDEL1 pathway regulates cilia disassembly.
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U2 - 10.1242/jcs.259999
DO - 10.1242/jcs.259999
M3 - Article
C2 - 36254578
AN - SCOPUS:85141889638
SN - 0021-9533
VL - 135
JO - The Quarterly journal of microscopical science
JF - The Quarterly journal of microscopical science
IS - 21
M1 - jcs259999
ER -