Localization of acetylcholine-related molecules in the retina: implication of the communication from photoreceptor to retinal pigment epithelium.

Localization of acetylcholine-related molecules in the retina: implication of the communication from photoreceptor to retinal pigment epithelium.
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DOI:
10.1371/journal.pone.0042841
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Ishizaki Y
Ishizaki Y
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Matsumoto H;Shibasaki K;Uchigashima M;Koizumi A;Kurachi M;Moriwaki Y;Misawa H;Kawashima K;Watanabe M;Kishi S;Ishizaki Y

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长期以来,人们一直推测特定的信号从光感受器传递到视网膜色素上皮(RPE)。然而,这些信号尚未被发现。在这项研究中,我们研究了视网膜表达和定位的乙酰胆碱相关分子作为这些信号的假定候选人。以往的研究表明,α7烟碱型乙酰胆碱受体(nAChRs)存在于视网膜色素上皮细胞的微绒毛中,包裹着感光细胞外节(OS)的顶端。分泌型哺乳动物白细胞抗原6/尿激酶型纤溶酶原激活物受体相关蛋白-1(SLURP-1)是α7 nAChR的正变构调节剂。因此,我们首先关注SLURP-1的表达。SLURP-1 mRNA在由感光细胞体组成的外核层中表达。SLURP-1免疫反应性与视紫红质和S-视蛋白在光感受器OS中共定位,而胆碱乙酰转移酶(ChAT)和高亲和力胆碱转运蛋白(CHT-1)也在光感受器OS中表达。免疫电镜证实SLURP-1主要定位于光感受器OS的质膜上。1在光感受器细胞体中合成并转运至光感受器OS,在那里也可以分泌SLURP-1。我们的研究结果表明,光感受器OS通过神经递质如ACh和SLURP-1进行通信,而RPE细胞可能通过其微绒毛中的α7 nAChR接收这些信号。
It has been long speculated that specific signals are transmitted from photoreceptors to the retinal pigment epithelium (RPE). However, such signals have not been identified. In this study, we examined the retinal expression and localization of acetylcholine-related molecules as putative candidates for these signals. Previous reports revealed that α7 nicotinic acetylcholine receptors (nAChRs) are present in the microvilli of RPE cells that envelope the tips of photoreceptor outer segments (OS). Secreted mammalian leukocyte antigen 6/urokinase-type plasminogen activator receptor-related protein-1 (SLURP-1) is a positive allosteric modulator of the α7 nAChR. Therefore, we first focused on the expression of SLURP-1. SLURP-1 mRNA was expressed in the outer nuclear layer, which is comprised of photoreceptor cell bodies. SLURP-1 immunoreactivity co-localized with rhodopsin and S-opsin in photoreceptor OS, while choline acetyltransferase (ChAT) and high affinity choline transporter (CHT-1) were also expressed in photoreceptor OS. Immunoelectron microscopy identified that the majority of SLURP-1 was localized to the plasma membranes of photoreceptor OS. These results provide evidence that SLURP-1 is synthesized in photoreceptor cell bodies and transported to photoreceptor OS, where SLURP-1 may also be secreted. Our findings suggest that photoreceptor OS communicate via neurotransmitters such as ACh and SLURP-1, while RPE cells might receive these signals through α7 nAChRs in their microvilli.
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