Department of Neuroscience, University of Texas-Austin, 100 E. 24th St., Austin, TX, 78712, USA.
Department of Molecular Physiology and Biophysics and Otolaryngology Head-Neck Surgery, Iowa Neuroscience Institute, Pappajohn Biomedical Institute, University of Iowa, Iowa City, Iowa, 52242, USA.
Sci Rep. 2023 Feb 14;13(1):2608. doi: 10.1038/s41598-023-29622-9.
Caldendrin is a Ca binding protein that interacts with multiple effectors, such as the Ca1 L-type Ca channel, which play a prominent role in regulating the outgrowth of dendrites and axons (i.e., neurites) during development and in response to injury. Here, we investigated the role of caldendrin in Ca1-dependent pathways that impinge upon neurite growth in dorsal root ganglion neurons (DRGNs). By immunofluorescence, caldendrin was localized in medium- and large- diameter DRGNs. Compared to DRGNs cultured from WT mice, DRGNs of caldendrin knockout (KO) mice exhibited enhanced neurite regeneration and outgrowth. Strong depolarization, which normally represses neurite growth through activation of Ca1 channels, had no effect on neurite growth in DRGN cultures from female caldendrin KO mice. Remarkably, DRGNs from caldendrin KO males were no different from those of WT males in terms of depolarization-dependent neurite growth repression. We conclude that caldendrin opposes neurite regeneration and growth, and this involves coupling of Ca1 channels to growth-inhibitory pathways in DRGNs of females but not males.
钙调蛋白是一种与多种效应器相互作用的 Ca 结合蛋白，如 Ca1 L 型 Ca 通道，在发育过程中调节树突和轴突（即神经突）的生长以及对损伤的反应中起着重要作用。在这里，我们研究了钙调蛋白在钙依赖性途径中的作用，这些途径会影响背根神经节神经元（DRGN）中的神经突生长。通过免疫荧光，钙调蛋白定位于中大和大直径的 DRGN 中。与 WT 小鼠来源的 DRGN 相比，钙调蛋白敲除（KO）小鼠的 DRGN 表现出增强的神经突再生和生长。强去极化通常通过激活 Ca1 通道来抑制神经突生长，但对雌性钙调蛋白 KO 小鼠来源的 DRGN 培养物中的神经突生长没有影响。值得注意的是，钙调蛋白 KO 雄性的 DRGN 在去极化依赖性神经突生长抑制方面与 WT 雄性没有区别。我们得出结论，钙调蛋白拮抗神经突再生和生长，这涉及到 Ca1 通道与雌性 DRGN 中生长抑制途径的偶联，但不是雄性。
