Laporte Jocelyn, Bedez Florence, Bolino Alessandra, Mandel Jean-Louis
IGBMC, CNRS/INSERM.ULP, Illkirch, France.
Hum Mol Genet. 2003 Oct 15;12 Spec No 2:R285-92. doi: 10.1093/hmg/ddg273. Epub 2003 Aug 12.
The myotubularin family is a large eukaryotic group within the tyrosine/dual-specificity phosphatase super-family (PTP/DSP). Among the 14 human members, three are mutated in genetic diseases: myotubular myopathy and two forms of Charcot-Marie-Tooth neuropathy. We present an analysis of the myotubularin family in sequenced genomes. The myotubularin family encompasses catalytically active and inactive phosphatases, and both classes are well conserved from nematode to man. Catalytically active myotubularins dephosphorylate phosphatidylinositol 3-phosphate (PtdIns3P) and PtdIns3,5P2, leading to the production of PtdIns and PtdIns5P. This activity may be modulated by direct interaction with catalytically inactive myotubularins. These phosphoinositides are signaling molecules that are notably involved in vacuolar transport and membrane trafficking. Myotubularins are thus proposed to be implicated in these cellular mechanisms, and recent observations on myotubularins homologues in the nematode Caenorhabditis elegans indicate a role in endocytosis.
肌管素家族是酪氨酸/双特异性磷酸酶超家族（PTP/DSP）中的一个大型真核生物类群。在14个人类成员中，有3个在遗传性疾病中发生了突变：肌管性肌病和两种形式的夏科-马里-图斯神经病变。我们对已测序基因组中的肌管素家族进行了分析。肌管素家族包括具有催化活性和无催化活性的磷酸酶，这两类在从线虫到人类的过程中都得到了很好的保守。具有催化活性的肌管素使磷脂酰肌醇3-磷酸（PtdIns3P）和磷脂酰肌醇3,5-二磷酸（PtdIns3,5P2）去磷酸化，导致磷脂酰肌醇（PtdIns）和磷脂酰肌醇5-磷酸（PtdIns5P）的产生。这种活性可能通过与无催化活性的肌管素直接相互作用而受到调节。这些磷酸肌醇是信号分子，特别参与液泡运输和膜 trafficking。因此，肌管素被认为与这些细胞机制有关，最近对线虫秀丽隐杆线虫中肌管素同源物的观察表明其在内吞作用中起作用。
