Calcium-independent receptor of alpha-latrotoxin (CIRL-1) is an adhesion G protein-coupled receptor implicated in the regulation of exocytosis. CIRL-1 biosynthesis involves constitutive proteolytic processing that takes place in the endoplasmic reticulum, requires the receptor's GPS domain, and yields heterologous two-subunit receptor complexes. It was proposed that the GPS-directed cleavage is based on cis-autoproteolysis. In this study, we demonstrate that activators of protein kinase C - PMA and ionomycin, can inhibit the cleavage of CIRL-1 precursor in transfected cells. Both reagents also downregulate trafficking of CIRL-1 to the cell surface that results in accumulation of the uncleaved receptor precursor inside the cells. Experiments with a non-cleavable soluble mutant of CIRL-1 showed that the downregulation of the receptor trafficking is independent of its cleavage. Our data suggest that the GPS proteolysis of CIRL-1 is not a purely autocatalytic process and may involve auxiliary proteins or factors that become available in the course of CIRL-1 trafficking.

中文翻译：

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监管CIRL-1蛋白水解和运输。

钙独立的α-Latotoxin受体（CIRL-1）是一种粘附G蛋白偶联受体，参与胞吐作用的调节。CIRL-1生物合成涉及内质网中发生的组成性蛋白水解过程，需要受体的GPS域，并产生异源的两个亚基受体复合物。有人提出，GPS定向的裂解是基于顺式自蛋白水解的。在这项研究中，我们证明了蛋白激酶C-PMA和离子霉素的激活剂可以抑制CIRL-1前体在转染细胞中的裂解。两种试剂还下调CIRL-1到细胞表面的运输，导致未裂解的受体前体在细胞内积累。用CIRL-1不可裂解的可溶性突变体进行的实验表明，受体运输的下调与它的裂解无关。我们的数据表明CIRL-1的GPS蛋白质水解不是纯粹的自催化过程，可能涉及辅助蛋白质或在CIRL-1贩运过程中变得可用的因子。