Scriver C R, Tenenhouse H S
Ann N Y Acad Sci. 1985;456:384-97. doi: 10.1111/j.1749-6632.1985.tb14889.x.
Membranes are organelles of homeostasis that control flux and distribution of molecules in cells. Carriers that mediate flux are gene products; mutations that modify carriers are probes that identify their function. Mutations can provide categorical taxonomies of membrane carriers; in higher organisms they can also identify location and characteristics of carriers. Mendelian human phenotypes reveal at least three different systems for the cationic amino acids (lys, orn, arg) segregated in brush-border (BBM) and basolateral (BLM) membranes of intestinal and renal epithelia; carrier(s) in parenchymal cells (e.g. fibroblasts) are not homologous. At least two gene products for phosphate reabsorption in nephron are revealed by X-linked and autosomal phenotypes; BBM and BLM also contain different forms of the carrier. Mutation reveals two forms of renal glucose reabsorption; the carriers are segregated in different proximal nephron segments. Mutations are potential probes for characterizing both the cellular pathways for synthesis, differentiation, insertion, segregation, turnover, and immobilization of membrane carrier proteins, and the mechanisms by which their function is altered.
膜是体内平衡的细胞器，可控制细胞内分子的通量和分布。介导通量的载体是基因产物；修饰载体的突变是确定其功能的探针。突变可以提供膜载体的分类学；在高等生物中，它们还可以确定载体的位置和特征。孟德尔人类表型揭示了至少三种不同的阳离子氨基酸（赖氨酸、鸟氨酸、精氨酸）系统，它们分别存在于肠道和肾上皮细胞的刷状缘（BBM）和基底外侧（BLM）膜中；实质细胞（如成纤维细胞）中的载体不同源。X连锁和常染色体表型揭示了肾单位中至少两种参与磷酸盐重吸收的基因产物；BBM和BLM也含有不同形式的载体。突变揭示了两种形式的肾葡萄糖重吸收；载体分布在不同的近端肾单位节段。突变是表征膜载体蛋白合成、分化、插入、分离、周转和固定的细胞途径以及其功能改变机制的潜在探针。
