Atiba-Davies Margaret, Noben-Trauth Konrad
Section on Neurogenetics, Laboratory of Molecular Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, 5 Research Court, Rockville, MD 20850, USA.
Biochim Biophys Acta. 2007 Aug;1772(8):1028-31. doi: 10.1016/j.bbadis.2007.01.007. Epub 2007 Jan 23.
TRPML3 (also known as mucolipin-3, MCOLN3) belongs to the small family of TRPML ion channel proteins. The mammalian Trpml3 gene encodes a protein of 553 amino acids with short amino and carboxy termini and a transient receptor potential motif spanning from the third to the sixth trans membrane domain. Dominant mutant alleles of Trpml3 cause hearing loss, circling behaviour, pigmentation defects and embryonic lethality in the varitint-waddler (Va) mouse. In the inner ear these mutations cause a reduction or loss of endocochlear potentials, compound action potentials, and auditory-evoked brain stem responses. The hearing phenotype is associated with defects in the cochlea that include disorganization and fusion of stereocilia, distortions at the apical and distal regions of inner and outer hair cells, and loss of pigmented intermediate cells in the stria vascularis. In hair cells the TRPML3 protein is targeted to cytoplasmic vesicles and to the plasma membrane of stereocilia. Both the sub-cellular localization of TRPML3 and the mutant phenotype suggest that TRPML3 is critical for stereocilia bundle formation during development and may function during endocytosis or exocytosis.
瞬时受体电位黏蛋白3（TRPML3，也称为黏脂蛋白3，MCOLN3）属于TRPML离子通道蛋白的小家族。哺乳动物的Trpml3基因编码一种由553个氨基酸组成的蛋白质，其氨基末端和羧基末端较短，且具有一个从第三个跨膜结构域延伸至第六个跨膜结构域的瞬时受体电位基序。Trpml3的显性突变等位基因会导致瓦廷特-沃德勒（Va）小鼠出现听力丧失、转圈行为、色素沉着缺陷和胚胎致死。在内耳中，这些突变会导致内淋巴电位、复合动作电位和听觉诱发脑干反应降低或丧失。听力表型与耳蜗缺陷有关，包括静纤毛的紊乱和融合、内外毛细胞顶端和远端区域的畸变以及血管纹中色素沉着中间细胞的丧失。在毛细胞中，TRPML3蛋白定位于细胞质囊泡和静纤毛的质膜。TRPML3的亚细胞定位和突变表型均表明，TRPML3在发育过程中对静纤毛束的形成至关重要，并且可能在胞吞作用或胞吐作用中发挥作用。
