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PreprintCited by 9Microtubule and mitosis dynamicsGenetic and Kidney Cyst DiseasesHeterocyclic Compound Synthesis and Bioactivity

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CEP41, a ciliopathy-linked centrosomal protein, regulates microtubule assembly and cell proliferation

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Prassanawar, Shweta Shyam, Sarkar, Tuhin, Panda, Dulal·2023·Journal of Cell Science
DOI 10.1101/2023.12.22.573068

Preprint — published as 10.1242/jcs.261927 · Paper page

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Abstract

Centrosomal proteins play pivotal roles in orchestrating microtubule dynamics, and their dysregulation leads to disorders, including cancer and ciliopathies. Understanding the multifaceted roles of centrosomal proteins is vital to comprehend their involvement in disease development. Here, we report novel cellular functions of CEP41, a centrosomal and ciliary protein implicated in Joubert syndrome. We show that CEP41 is an essential microtubule-associated protein with microtubule-stabilizing activity. Purified CEP41 binds to preformed microtubules, promotes microtubule nucleation, and suppresses microtubule disassembly. When overexpressed in cultured cells, CEP41 localizes to microtubules and promotes microtubule bundling. Conversely, shRNA-mediated knockdown of CEP41 disrupts the interphase microtubule network and delays microtubule reassembly, emphasizing its role in microtubule organization. Further, we demonstrate that CEP41’s association with microtubules relies on its conserved rhodanese homology domain (RHOD) and the N-terminal region. Interestingly, a disease-causing mutation in the RHOD domain impairs CEP41-microtubule interaction. Moreover, depletion of CEP41 inhibits cell proliferation and disrupts cell cycle progression, suggesting its potential involvement in cell cycle regulation. These insights into the cellular functions of CEP41 hold promise for unraveling the impact of its mutations in ciliopathies. Summary: A novel role of CEP41 as a microtubule-associated protein that promotes microtubule assembly and regulates cell cycle progression could offer insights into the development of ciliopathies.

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Metadata

Authors
Prassanawar, S. S., Sarkar, T., & Panda, D.
Affiliations
Indian Institute of Technology Bombay (IN)
Corresponding author
Panda, Dulal
ORCID
Venue
Journal of Cell Science
Publisher
openRxiv
Published
2023-12-22
Volume
137
Issue
13
ISSN
0021-9533 (ISSN-L)
DOI
10.1101/2023.12.22.573068
OpenAlex
W4399401405
Cited by
9
References
1
Citations by year
2026: 3 · 2025: 4 · 2024: 2
FWCI
2.03
Type
journal article
Language
en
Open access
Locations
  • Journal of Cell Science (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed (publishedVersion)
Funders
  • Indian Institute of Science
  • Department of Science and Technology, Ministry of Science and Technology, India (J.C.B./2019/000016)
  • Council of Scientific and Industrial Research, India
  • Indian Institute of Technology Bombay
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
  • Physical Sciences › Chemistry › Organic Chemistry › Heterocyclic Compound Synthesis and Bioactivity
Keywords
centrosomal proteins, ciliopathies, Joubert syndrome, microtubule assembly, microtubule stabilization, microtubule bundling, microtubule nucleation, microtubule disassembly, cell proliferation, cell cycle regulation, microtubule reassembly
MeSH terms
Abnormalities, Multiple, Ciliopathies, Animals, Cell Cycle, Cerebellum, Cilia, Eye Abnormalities, Humans, Microtubule-Associated Proteins, Microtubules, Protein Binding, Retina, Centrosome, Cell Cycle Proteins, Cell Proliferation, Kidney Diseases, Cystic, HEK293 Cells

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