Myotubularin-related (MTMR) phospholipid phosphatase proteins in the peripheral nervous system
Myotubularin-related (MTMR) phospholipid phosphatase proteins in the peripheral nervous system
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DOI：
10.1007/s12035-007-0031-0
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发表时间：
2007-06-01
影响因子：
5.1
通讯作者：
Bolino, Alessandra
中科院分区：
文献类型：
--
作者：
Bolis, Annalisa;Zordan, Paola;Bolino, Alessandra
肌管蛋白相关蛋白(MTMR)是一个广泛表达的磷酸酶家族，在人类中有14个成员，其中8个是催化活性磷酸酶，6个是非催化活性磷酸酶。活性MTMR对PtdIns3P和PtdIns(3，5)P-2磷脂酰肌醇(PPIN)均具有3-磷酸酶活性，提示参与了细胞内转运和膜动态平衡。在MTMR中，催化活性的MTMR2和非活性的MTMR13在神经中具有非冗余功能。MTMR2或MTMR13的丢失分别导致4B1型和B2型Charcot-Marie-Tooth神经病，其特征是脱髓鞘和称为髓鞘外折的髓鞘多余环。在mtmr2缺失的小鼠神经中，这些异常折叠发生在出生后3-4周，此时髓鞘形成，雪旺细胞仍在延长，以达到最终的节间长度。此外，雪旺细胞中的Mtmr2特异性消融既充分也是必要的，可以激发髓鞘外折叠的CMT4B1。MTMR2磷脂磷酸酶可能调节雪旺细胞在生后神经发育过程中的胞内转运事件和膜稳态。在这篇综述中，我们将讨论关于MTMR家族的最新发现，主要集中在MTMR2和MTMR13以及它们在雪旺细胞生物学中的可能作用。
Myotubularin-related proteins ( MTMRs) constitute a broad family of ubiquitously expressed phosphatases with 14 members in humans, of which eight are catalytically active phosphatases, while six are catalytically inactive. Active MTMRs possess 3-phosphatase activity toward both PtdIns3P and PtdIns( 3, 5) P-2 poliphosphoinositides ( PPIn), suggesting an involvement in intracellular trafficking and membrane homeostasis. Among MTMRs, catalytically active MTMR2 and inactive MTMR13 have a nonredundant function in nerve. Loss of either MTMR2 or MTMR13 causes Charcot-Marie-Tooth type 4B1 and B2 neuropathy, respectively, characterized by demyelination and redundant loops of myelin known as myelin outfoldings. In Mtmr2-null mouse nerves, these aberrant foldings occur at 3-4 weeks after birth, a time when myelination is established, and Schwann cells are still elongating to reach the final internodal length. Moreover, Mtmr2-specific ablation in Schwann cells is both sufficient and necessary to provoke CMT4B1 with myelin outfoldings. MTMR2 phospholipid phosphatase might regulate intracellular trafficking events and membrane homeostasis in Schwann cells during postnatal nerve development. In this review, we will discuss recent findings on the MTMR family with a major focus on MTMR2 and MTMR13 and their putative role in Schwann cell biology.