Calcium selective channel TRPV6: Structure, function, and implications in health and disease.
Calcium selective channel TRPV6: Structure, function, and implications in health and disease.
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DOI：
10.1016/j.gene.2022.146192
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发表时间：
2022-04-05
期刊：
影响因子：
3.5
通讯作者：
Peng JB
中科院分区：
文献类型：
--
作者：
Khattar V;Wang L;Peng JB
钙选择性通道TRPV6（Transient Receptor Potential Channel family，Vanilloid subfamily member 6）属于TRP阳离子通道家族，在跨细胞钙转运、细胞内钙重摄取以及维持局部低钙环境等生物学过程中发挥重要作用。最近的晶体和冷冻电子显微镜为基础的结构TRPV6揭示了机制的见解，蛋白质如何实现钙离子的选择性，渗透和失活的钙调蛋白。TRPV6蛋白在一系列上皮组织如肠、肾、胎盘、附睾和外分泌腺如胰腺、前列腺和唾液腺、汗液和乳腺中表达。TRPV6基因是活性形式维生素D的直接转录靶点，并被有效调节以满足身体对Ca2+的需求。此外，TRPV6还受膳食Ca2+水平以及妊娠和哺乳等生理条件的调节。TRPV6功能丧失的遗传模型显示高钙尿、骨髓密度降低、体重增加不足、生育能力降低，在某些情况下还显示脱发。该模型还揭示了该通道在维持母胎Ca 2+转运和附睾腔中的低Ca 2+环境中起着不可或缺的作用，这对男性生育力至关重要。最近，TRPV6基因的功能缺失突变与一过性新生儿甲状旁腺功能亢进和早发性慢性胰腺炎有关。TRPV6在广泛的人类恶性肿瘤中过表达，并且其上调与选定癌症中的肿瘤侵袭性、转移和较差的存活率密切相关。本文综述了TRPV6的表达、结构、生物物理特性、功能、多态性和调控等方面的研究进展。异常表达，多态性和功能障碍，这种蛋白质与人类疾病也进行了讨论。
Calcium-selective channel TRPV6 (Transient Receptor Potential channel family, Vanilloid subfamily member 6) belongs to the TRP family of cation channels and plays critical roles in transcellular calcium (Ca2+) transport, reuptake of Ca2+ into cells, and maintaining a local low Ca2+ environment for certain biological processes. Recent crystal and cryo-electron microscopy-based structures of TRPV6 have revealed mechanistic insights on how the protein achieves Ca2+ selectivity, permeation, and inactivation by calmodulin. The TRPV6 protein is expressed in a range of epithelial tissues such as the intestine, kidney, placenta, epididymis, and exocrine glands such as the pancreas, prostate and salivary, sweat, and mammary glands. The TRPV6 gene is a direct transcriptional target of the active form of vitamin D and is efficiently regulated to meet the body’s need for Ca2+ demand. In addition, TRPV6 is also regulated by the level of dietary Ca2+ and under physiological conditions such as pregnancy and lactation. Genetic models of loss of function in TRPV6 display hypercalciuria, decreased bone marrow density, deficient weight gain, reduced fertility, and in some cases alopecia. The models also reveal that the channel plays an indispensable role in maintaining maternal-fetal Ca2+ transport and low Ca2+ environment in the epididymal lumen that is critical for male fertility. Most recently, loss of function mutations in TRPV6 gene is linked to transient neonatal hyperparathyroidism and early onset chronic pancreatitis. TRPV6 is overexpressed in a wide range of human malignancies and its upregulation is strongly correlated to tumor aggressiveness, metastasis, and poor survival in selected cancers. This review summarizes the current state of knowledge on the expression, structure, biophysical properties, function, polymorphisms, and regulation of TRPV6. The aberrant expression, polymorphisms, and dysfunction of this protein linked to human diseases are also discussed.
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影响因子：
9.8
作者：
Akey JM;Eberle MA;Rieder MJ;Carlson CS;Shriver MD;Nickerson DA;Kruglyak L
通讯作者：
Kruglyak L
影响因子：
3.7
作者：
Azarpeykan S;Dittmer KE;Marshall JC;Perera KC;Gee EK;Acke E;Thompson KG
通讯作者：
Thompson KG
DOI：
10.1186/1477-7827-10-66
发表时间：
2012-08-29
期刊：
Reproductive biology and endocrinology : RB&E
影响因子：
--
作者：
Sprekeler N;Kowalewski MP;Boos A
通讯作者：
Boos A
影响因子：
3.3
作者：
Arbabian, Atousa;Iftinca, Mircea;Coscoy, Sylvie
通讯作者：
Coscoy, Sylvie
影响因子：
3.7
作者：
Hughes DA;Tang K;Strotmann R;Schöneberg T;Prenen J;Nilius B;Stoneking M
通讯作者：
Stoneking M