PKD2-like proteins target Chlamydomonas PKD2 to distinct subciliary regions
PKD2-like proteins target Chlamydomonas PKD2 to distinct subciliary regions Poulomi Das
Proc Natl Acad Sci U S A. 2026 Oct 6;123(40):e2524371123. doi: 10.1073/pnas.2524371123. Epub 2026 Sep 29.
ABSTRACT
Many motile and sensory functions of cilia and flagella depend on the precise localization of transmembrane proteins within the ciliary membrane. Rather than being uniformly distributed, these proteins are often targeted to specific subciliary regions along the length or circumference of cilia. Here, we use genome editing and in vivo imaging to dissect the spatial organization of the channel protein PKD2 in Chlamydomonas cilia. MST3, a PKD2-like protein with five transmembrane helices (5TMH), is localized exclusively to the distal cilium, where it is essential for the localization of PKD2 and the formation of the hair-like mastigonemes. MST3, however, is dispensable for PKD2 assembly in the proximal cilium. In contrast, the PKD2-like 5TMH protein Proximal PKD2 Interactor (PPI) resides in the proximal cilium, where it is required for PKD2 assembly; ppi mutants retain distal PKD2 and mastigonemes. In mst3 ppi double knockouts, both proximal and distal PKD2 are absent, revealing that MST3 and PPI organize PKD2 into distal and proximal regions. Further, PKD2 colocalizes and comigrates with PKD2-like protein 1 (PLP1), another 5TMH protein, in cilia, indicating that they are present together in a complex. While plp1 mutants swim largely normally, mst3 and, to a lesser degree, ppi mutants swim with reduced velocity, indicating a functional specialization of the different ciliary PKD2 complexes. Thus, Chlamydomonas PKD2 associates with one of several 5TMH proteins to form spatially and genetically distinct PKD2 complexes, while also establishing their longitudinal distribution in cilia.
PMID:42809393 | DOI:10.1073/pnas.2524371123
Many motile and sensory functions of cilia and flagella depend on the precise localization of transmembrane proteins within the ciliary membrane. Rather than being uniformly distributed, these proteins are often targeted to specific subciliary regions along the length or circumference of cilia. Here, we use genome editing and in vivo imaging to dissect the spatial organization of the channel protein PKD2 in Chlamydomonas cilia. MST3, a PKD2-like protein with five transmembrane helices (5TMH), is… [#item_author]
