MiniBAR/KIAA0355 is a dual Rac and Rab effector required for ciliogenesis

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Shaughnessy, Ronan | Serres, Murielle | Escot, Sophie | Hammich, Hussein | Cuvelier, Frédérique | Salles, Audrey | Rocancourt, Murielle | Verdon, Quentin | Gaffuri, Anne-Lise | Sourigues, Yannick | Malherbe, Gilles | Velikovsky, Leonid | Chardon, Florian | Tinevez, Jean-Yves | Callebaut, Isabelle | Formstecher, Etienne | Houdusse, Anne | David, Nicolas | Pylypenko, Olena | Echard, Arnaud

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Posted July 24, 2023 on bioRxiv.. Cilia protrude from the cell surface and play critical roles in in-tracellular signaling, environmental sensing and development. Actin-dependent contractility and intracellular trafficking are both required for ciliogenesis, but little is known about how these processes are coordinated. Here, we identified a Rac1-and Rab35-binding protein with a truncated BAR domain that we named MiniBAR (aka KIAA0355/GARRE) which plays a key role in ciliogenesis. MiniBAR colocalizes with Rac1 and Rab35 at the plasma membrane and on intracellular vesicles traffick-ing to the ciliary base and exhibits remarkable fast pulses at the ciliary membrane. MiniBAR depletion leads to short cilia resulting from abnormal Rac-GTP/Rho-GTP levels, increased acto-myosin-II-dependent contractility together with defective trafficking of IFT88 and ARL13B into cilia. MiniBAR-depleted zebrafish embryos display dysfunctional short cilia and hall-marks of ciliopathies including left-right asymmetry defects. Thus, MiniBAR is a unique dual Rac and Rab effector that con-trols both actin cytoskeleton and membrane trafficking for cili-ogenesis.

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