Document Type
Article
Publication Title
iScience
Publication Date
2024
Keywords
Biochemistry, molecular biology, cell biology
Abstract
Primary cilia are essential signaling organelles that protrude from most cells in the body. Heterodimeric kinesin-2 (KIF3A/KIF3B/KAP3) powers several intracellular transport processes, including intraflagellar transport (IFT), essential for ciliogenesis. A long-standing question is how a motor protein is differentially regulated for specific cargos. Since phosphorylation of the KIF3A tail domain was suggested to regulate the activity of kinesin-2 for ciliogenesis, similarly as for the cytosolic cargo N-Cadherin, we set out to map the phosphosites involved in this regulation. Using well-characterized Kif3a−/−; Kif3b−/− mouse embryonic fibroblasts, we performed ciliogenesis rescue assays with a library of phosphomimetic mutants comprising all predicted phosphosites in the KIF3A tail domain. In contrast to previous reports, we found that KIF3A tail domain phosphorylation is dispensable for ciliogenesis in mammals. Thus, mammalian kinesin-2 is differently regulated for IFT than currently thought, consistent with the idea of differential regulation for ciliary and cytosolic cargo.
Funding Source
This work was supported by the National Institute of General Medical Sciences of the National Institutes of Health under award numbers R15GM137248 (to M.F.E.) and R35GM147641 (to M.F.E.), an internal Illinois State University grant to M.F.E. (URG-NFIG) and an internal Weigel Grant to A.S.F. The content is solely the authors' responsibility and does not necessarily represent the official views of the National Institutes of Health.
Recommended Citation
Ayoola S. Fasawe, Jessica M. Adams, & Martin F. Engelke, "KIF3A tail domain phosphorylation is not required for ciliogenesis in mouse embryonic fibroblasts," iScience, 27, Issue 3, (2024): 109149. https://doi.org/10.1016/j.isci.2024.109149.
DOI
https://doi.org/10.1016/j.isci.2024.109149
Supplemental information
Comments
First published in iScience 27, no. 3, (15 March 2024): 109149. https://doi.org/10.1016/j.isci.2024.109149.
This open access article is published under a CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) .