Deficiency of CAMSAP2 impairs olfaction and the morphogenesis of mitral cells

In developing olfactory bulb (OB), mitral cells (MCs) remodel their dendrites to establish the precise olfactory circuit, and these circuits are critical for individuals to sense odors and elicit behaviors for survival. However, how microtubules (MTs) participate in the process of dendritic remodeling remains elusive. Here, we reveal that calmodulin-regulated spectrin-associated proteins (CAMSAPs), a family of proteins that bind to the minus-end of the noncentrosomal MTs, play a crucial part in the development of MC dendrites. We observed that Camsap2 knockout (KO) males are infertile while the reproductive tract is normal. Further study showed that the infertility was due to the severe defects of mating behavior in male mice. Besides, mice with loss-of-function displayed defects in the sense of smell. Furthermore, we found that the deficiency of CAMSAP2 impairs the classical morphology of MCs, and the CAMSAP2-dependent dendritic remodeling process is responsible for this defect. Thus, our findings demonstrate that CAMSAP2 plays a vital role in regulating the development of MCs. Synopsis CAMSAP2, the non-centrosomal microtubule binding protein, has critical roles in the development of mitral cells, establishment of the olfactory circuitry and olfactory-guided mating behavior. CAMSAP2 knockout male mice exhibit infertility. Deficiency in CAMSAP2 impairs olfaction. Deficiency in CAMSAP2 impairs olfactory-guided mating behavior of male mice. CAMSAP2 plays a critical role in the development of mitral cells in the olfactory bulb. CAMSAP2, the non-centrosomal microtubule binding protein, has critical roles in the development of mitral cells, establishment of the olfactory circuitry and olfactory-guided mating behavior.