Temporal Vestibular Deficits in synaptojanin 1 (synj1) Mutants.
Temporal Vestibular Deficits in synaptojanin 1 (synj1) Mutants.
复制标题
DOI：
10.3389/fnmol.2020.604189
复制
发表时间：
2020
影响因子：
4.8
通讯作者：
Nicolson T
中科院分区：
文献类型：
--
作者：
Gao Y;Nicolson T
脂质磷酸酶synaptojanin 1（synj1）是内吞隔室网格蛋白外套解体所必需的。在神经元中，这种活性是胞吞膜再循环进入突触小泡所必需的。斑马鱼synj1基因的突变已被证明会破坏感觉毛细胞中带状突触的活性。经过长时间的机械刺激毛细胞，相位锁定传入神经活动和突触囊泡的自发释放的恢复减少synj1突变体。据推测，作为这些突触缺陷的行为后果，synj1突变体无法保持直立姿势。为了探讨前庭功能与姿势控制synj1突变体，我们开发了一种方法来评估前庭脊髓反射（VSR）的幼虫。我们通过旋转头部和记录尾部运动来诱发VSR。如所预期的，VSR在缺乏内耳功能的pcdhl5a和lhfpl5a突变体中完全不存在。相反地，具有侧线器官功能的选择性丧失的lhfpl5b突变体具有正常的VSR，表明该器官的毛细胞对该反射没有贡献。与机械转导突变体相反，synj1突变体在头部旋转的初始周期期间产生正常的尾部运动。响应的幅度和时间方面都没有改变。然而，经过几次旋转后，synj1突变体中的VSR强烈减少或缺失。突变的synj1幼虫能够恢复，但在synj1突变体中，长时间刺激后VSR再现所需的时间显著增加。总的来说，这些数据表明synj1功能丧失引起的突触缺陷与行为相关。我们的研究结果表明，在突触囊泡回收的缺陷引起疲劳的带状突触和可能的VS电路的其他突触，导致姿势控制的损失。
The lipid phosphatase synaptojanin 1 (synj1) is required for the disassembly of clathrin coats on endocytic compartments. In neurons such activity is necessary for the recycling of endocytosed membrane into synaptic vesicles. Mutations in zebrafish synj1 have been shown to disrupt the activity of ribbon synapses in sensory hair cells. After prolonged mechanical stimulation of hair cells, both phase locking of afferent nerve activity and the recovery of spontaneous release of synaptic vesicles are diminished in synj1 mutants. Presumably as a behavioral consequence of these synaptic deficits, synj1 mutants are unable to maintain an upright posture. To probe vestibular function with respect to postural control in synj1 mutants, we developed a method for assessing the vestibulospinal reflex (VSR) in larvae. We elicited the VSR by rotating the head and recorded tail movements. As expected, the VSR is completely absent in pcdh15a and lhfpl5a mutants that lack inner ear function. Conversely, lhfpl5b mutants, which have a selective loss of function of the lateral line organ, have normal VSRs, suggesting that the hair cells of this organ do not contribute to this reflex. In contrast to mechanotransduction mutants, the synj1 mutant produces normal tail movements during the initial cycles of rotation of the head. Both the amplitude and temporal aspects of the response are unchanged. However, after several rotations, the VSR in synj1 mutants was strongly diminished or absent. Mutant synj1 larvae are able to recover, but the time required for the reappearance of the VSR after prolonged stimulation is dramatically increased in synj1 mutants. Collectively, the data demonstrate a behavioral correlate of the synaptic defects caused by the loss of synj1 function. Our results suggest that defects in synaptic vesicle recycling give rise to fatigue of ribbons synapses and possibly other synapses of the VS circuit, leading to the loss of postural control.
登录
查看更多内容
影响因子：
5.7
作者：
Bagnall MW;Schoppik D
通讯作者：
Schoppik D
DOI：
10.1083/jcb.150.3.589
发表时间：
2000-08-07
期刊：
The Journal of cell biology
影响因子：
--
作者：
Harris TW;Hartwieg E;Horvitz HR;Jorgensen EM
通讯作者：
Jorgensen EM
影响因子：
64.5
作者：
Dickman, DK;Horne, JA;Schwarz, TL
通讯作者：
Schwarz, TL
影响因子：
3.3
作者：
Andre, P;Pompeiano, O;Manzoni, D
通讯作者：
Manzoni, D
影响因子：
4.1
作者：
Kirola, Laxmi;Behari, Madhuri;Thelma, B. K.
通讯作者：
Thelma, B. K.