Wdr47 Controls Neuronal Polarization through the Camsap Family Microtubule Minus-End-Binding Proteins

Abstract

Highlights d Wdr47 ensures proper neuronal polarity both in vivo and in vitro d Wdr47 controls neuronal polarity by modulating regional microtubule dynamics d Wdr47 functions in unpolarized neurons through Camsap family proteins d The neuronal function of Wdr47 is required for neonatal mouse survival

Wdr47, Camsaps, and Katanin cooperate to generate ciliary central microtubules

“…concentrated Camsaps into the central lumen, where Camsaps stabilized the minus ends of the seeds to allow central MT elongation. As emerging evidence suggests that Wdr47, Camsaps, and Katanin also similarly impact neuronal polarization and axonal growth 14,15,17,40,41 , our findings indicate that the same pathway is used to properly generate and organize non-centrosomal MT arrays in polarized subcellular compartments such as the axon and motile cilium.…”

“…In this study, we demonstrated that three groups of interacting proteins, the WD40 repeat-containing Wdr47 (also called Nemitin) 14,36 , Camsaps, and the MT-servering enzyme Katanin 12,[37][38][39] , co-operated to achieve the initial central MT formation in mammalian multicilia. Katanin produces central MT seeds by severing the peripheral MTs.…”

“…We generated Wdr47-deficient mice by crossing Wdr47 knockout-first (Wdr47 Kof/+ ) mice with EIIa-Cre mice (Fig. 1f) 14 and analyzed the ciliary motility of cultured mEPCs 35 .…”

“…Wdr47-deficient mice die immediately after birth due to central nervous system defects 14 and were not suitable for the investigation. The Wdr47 Kof/Kof mice, however, are quite heterogeneous in viability: the majority of them die before P55 but the remaining mice live longer than P153 48 , probably due to variations in Wdr47 expression levels 14 . To maintain minimal levels of Wdr47 for mouse survival, we created Wdr47 Kof/mice and found that they were viable after birth.…”

“…Recently, calmodulin-regulated spectrin-associated proteins (Camsaps) have been found to stabilize free MT minus ends through direct binding to facilitate the rapid growth of the MT plus ends [10][11][12][13] . They function in the organization of non-centrosomal MT arrays in epithelial and neuronal cells [14][15][16][17][18] .…”