Developmental differences between cation-independent and cation-dependent mannose-6-phosphate receptors in rat brain at perinatal stages

P.S. Romano, L. Carvelli, A.C. López, G. Jofré, T. Sartor, M.A. Sosa
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引用次数: 12

Abstract

Mannose-6-phosphate receptors (MPRs) play a role in the selective transport of macromolecules bearing mannose-6-phosphate residue to lysosomes. To date, two types of MPRs have been described in most of cells and tissues: the cation-dependent (CD-MPR) and cation-independent mannose-6-phosphate receptor (CI-MPR). In order to elucidate their possible role in the central nervous system, the expression and binding properties of both MPRs were studied in rat brain along perinatal development. It was observed that the expression of CI-MPR decreases progressively from fetuses to adults, while the CD-MPR increases around the 10th day of birth, and maintains these values up to adulthood. Binding assays showed differences in the Bmax and KD values between the ages studied, and they did not correlate with the expression levels of both MPRs. Variations in lysosomal enzyme activities and expression of phosphomannosylated ligands during development correlated more with CD-MPR than with CI-MPR expression. These results suggest that both receptors play a different role in rat brain during perinatal development, being CD-MPR mostly involved in lysosome maturation.

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围产期大鼠脑中阳离子依赖型和阳离子依赖型甘露糖-6-磷酸受体的发育差异
甘露糖-6-磷酸受体(MPRs)在携带甘露糖-6-磷酸残基的大分子选择性转运到溶酶体中起作用。迄今为止,在大多数细胞和组织中已经描述了两种类型的mpr:阳离子依赖性(CD-MPR)和阳离子非依赖性甘露糖-6-磷酸受体(CI-MPR)。为了阐明它们在中枢神经系统中的可能作用,我们研究了这两种mpr在围生期大鼠脑中的表达和结合特性。从胎儿到成年,CI-MPR的表达逐渐降低,而CD-MPR的表达在出生第10天左右增加,并一直保持到成年。结合试验显示,研究年龄之间Bmax和KD值存在差异,且与两种MPRs的表达水平无关。发育过程中溶酶体酶活性和磷酸化配体表达的变化与CD-MPR的相关性大于与CI-MPR的相关性。这些结果表明,这两种受体在围产期大鼠脑发育过程中发挥不同的作用,CD-MPR主要参与溶酶体的成熟。
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