Institute of Molecular Medicine and Bioengineering, National Yang Ming Chiao Tung University, Hsinchu, Taiwan.
Department of Orthopedic Surgery, Changhua Christian Hospital, Changhua, Taiwan.
Elife. 2024 Jun 21;13:RP94547. doi: 10.7554/eLife.94547.
A functional nervous system is built upon the proper morphogenesis of neurons to establish the intricate connection between them. The microtubule cytoskeleton is known to play various essential roles in this morphogenetic process. While many microtubule-associated proteins (MAPs) have been demonstrated to participate in neuronal morphogenesis, the function of many more remains to be determined. This study focuses on a MAP called HMMR in mice, which was originally identified as a hyaluronan binding protein and later found to possess microtubule and centrosome binding capacity. HMMR exhibits high abundance on neuronal microtubules and altering the level of HMMR significantly affects the morphology of neurons. Instead of confining to the centrosome(s) like cells in mitosis, HMMR localizes to microtubules along axons and dendrites. Furthermore, transiently expressing HMMR enhances the stability of neuronal microtubules and increases the formation frequency of growing microtubules along the neurites. HMMR regulates the microtubule localization of a non-centrosomal microtubule nucleator TPX2 along the neurite, offering an explanation for how HMMR contributes to the promotion of growing microtubules. This study sheds light on how cells utilize proteins involved in mitosis for non-mitotic functions.
一个功能正常的神经系统是建立在神经元的正确形态发生之上的，以建立它们之间错综复杂的连接。微管细胞骨架在这个形态发生过程中起着各种重要的作用。虽然已经证明许多微管相关蛋白（MAPs）参与神经元形态发生，但仍有许多 MAP 的功能有待确定。本研究集中于一种在小鼠中称为 HMMR 的 MAP，它最初被鉴定为透明质酸结合蛋白，后来发现它具有微管和中心体结合能力。HMMR 在神经元微管上含量丰富，改变 HMMR 的水平会显著影响神经元的形态。HMMR 不像有丝分裂中的细胞那样局限于中心体（s），而是沿着轴突和树突定位到微管上。此外，瞬时表达 HMMR 增强了神经元微管的稳定性，并增加了沿着神经突生长微管的形成频率。HMMR 调节非中心体微管核蛋白 TPX2 在神经突上的微管定位，为 HMMR 如何促进生长微管提供了一个解释。本研究揭示了细胞如何利用参与有丝分裂的蛋白质来发挥非有丝分裂功能。
