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Published on: February 21, 2016
Deficiency of CAMSAP2 impairs olfaction and the morphogenesis of mitral cells
Zhengrong Zhou1,2, Xiaojuan Yang3,4, Aihua Mao5
1State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, 100101, Beijing, China. zrzhou@genetics.ac.cn.
Abstract:
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.
Insights
Calmodulin-regulated spectrin-associated proteins (CAMSAPs) are crucial for olfactory bulb development. CAMSAP2 deficiency impairs mitral cell dendritic remodeling, leading to infertility and defective sense of smell in mice.
Area of Science:
- Neuroscience
- Cell Biology
- Developmental Biology
Background:
- Olfactory bulb (OB) development involves mitral cell (MC) dendritic remodeling for precise olfactory circuit formation.
- Microtubules (MTs) are essential for neuronal development, but their role in MC dendritic remodeling is not fully understood.
- Calmodulin-regulated spectrin-associated proteins (CAMSAPs) bind to noncentrosomal MT minus-ends.
Purpose of the Study:
- To investigate the role of CAMSAPs in the development of olfactory bulb mitral cell dendrites.
- To elucidate the function of CAMSAP2 in olfactory circuit formation and associated behaviors.
Main Methods:
- Generated Camsap2 knockout (KO) mice to study loss-of-function phenotypes.
- Assessed reproductive behavior, mating success, and olfactory sense in KO mice.
- Examined the morphology of mitral cells and their dendritic structures in KO mice.
Main Results:
- Camsap2 KO males exhibited infertility due to severe mating behavior defects.
- Loss of CAMSAP2 function resulted in impaired sense of smell.
- CAMSAP2 deficiency led to abnormal mitral cell morphology and defective dendritic remodeling.
Conclusions:
- CAMSAP2 is vital for the proper development and dendritic remodeling of olfactory bulb mitral cells.
- CAMSAP2 plays a critical role in regulating olfactory-driven behaviors, including mating and odor perception.
- These findings highlight CAMSAP2 as a key regulator of neuronal circuit formation in the olfactory system.
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