State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, 100101, Beijing, China.
Neuroscience Center, Department of Basic Medical Sciences, Shantou University Medical College, 515041, Shantou, Guangdong, China.
EMBO Rep. 2024 Jul;25(7):2861-2877. doi: 10.1038/s44319-024-00166-x. Epub 2024 Jun 5.
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.
在嗅球（OB）的发育过程中，僧帽细胞（MC）重塑其树突以建立精确的嗅觉回路，而这些回路对于个体感知气味和引发生存行为至关重要。然而，微管（MT）如何参与树突重塑过程仍然难以捉摸。在这里，我们揭示了钙调蛋白调节 spectrin 相关蛋白（CAMSAPs），一组与非中心体 MT 的负端结合的蛋白质，在 MC 树突发育中起着关键作用。我们观察到 Camsap2 敲除（KO）雄性不育，而生殖道正常。进一步的研究表明，不育是由于雄性小鼠交配行为严重缺陷所致。此外，具有功能丧失的小鼠表现出嗅觉缺陷。此外，我们发现 CAMSAP2 的缺乏会损害 MC 的经典形态，并且 CAMSAP2 依赖性树突重塑过程是造成这种缺陷的原因。因此，我们的研究结果表明 CAMSAP2 在调节 MC 发育中起着至关重要的作用。
