Department of Molecular Cell Biology, Laboratory of Ion Channel Research, Campus Gasthuisberg, KU Leuven, Herestraat 49, B-3000 Leuven, Belgium.
Genome Biol. 2011;12(3):218. doi: 10.1186/gb-2011-12-3-218. Epub 2011 Mar 17.
The transient receptor potential (TRP) multigene superfamily encodes integral membrane proteins that function as ion channels. Members of this family are conserved in yeast, invertebrates and vertebrates. The TRP family is subdivided into seven subfamilies: TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPP (polycystin), TRPML (mucolipin), TRPA (ankyrin) and TRPN (NOMPC-like); the latter is found only in invertebrates and fish. TRP ion channels are widely expressed in many different tissues and cell types, where they are involved in diverse physiological processes, such as sensation of different stimuli or ion homeostasis. Most TRPs are non-selective cation channels, only few are highly Ca2+ selective, some are even permeable for highly hydrated Mg2+ ions. This channel family shows a variety of gating mechanisms, with modes of activation ranging from ligand binding, voltage and changes in temperature to covalent modifications of nucleophilic residues. Activated TRP channels cause depolarization of the cellular membrane, which in turn activates voltage-dependent ion channels, resulting in a change of intracellular Ca2+ concentration; they serve as gatekeeper for transcellular transport of several cations (such as Ca2+ and Mg2+), and are required for the function of intracellular organelles (such as endosomes and lysosomes). Because of their function as intracellular Ca2+ release channels, they have an important regulatory role in cellular organelles. Mutations in several TRP genes have been implicated in diverse pathological states, including neurodegenerative disorders, skeletal dysplasia, kidney disorders and pain, and ongoing research may help find new therapies for treatments of related diseases.
瞬时受体电位 (TRP) 多基因超家族编码作为离子通道的完整膜蛋白。该家族的成员在酵母、无脊椎动物和脊椎动物中都有保守。TRP 家族分为七个亚家族:TRPC(经典)、TRPV(香草酸)、TRPM(melastatin)、TRPP(多囊蛋白)、TRPML(粘脂素)、TRPA(锚蛋白)和 TRPN(NOMPC 样);后者仅存在于无脊椎动物和鱼类中。TRP 离子通道广泛表达于许多不同的组织和细胞类型,在这些组织和细胞类型中,它们参与多种生理过程,例如不同刺激的感觉或离子稳态。大多数 TRP 是非选择性阳离子通道,只有少数是高度 Ca2+选择性的,有些甚至对高度水合的 Mg2+离子具有通透性。该通道家族显示出多种门控机制,激活模式从配体结合、电压和温度变化到亲核残基的共价修饰不等。激活的 TRP 通道导致细胞膜去极化,这反过来又激活电压依赖性离子通道,导致细胞内 Ca2+浓度的变化;它们作为几种阳离子(如 Ca2+和 Mg2+)的跨细胞转运的守门员,并为细胞内细胞器(如内体和溶酶体)的功能所必需。由于它们作为细胞内 Ca2+释放通道的功能,它们在细胞细胞器中具有重要的调节作用。几种 TRP 基因的突变与多种病理状态有关,包括神经退行性疾病、骨骼发育不良、肾脏疾病和疼痛,正在进行的研究可能有助于为相关疾病的治疗找到新的治疗方法。