High density lipoprotein endocytosis by scavenger receptor SR-BII is clathrin-dependent and requires a carboxyl-terminal dileucine motif
High density lipoprotein endocytosis by scavenger receptor SR-BII is clathrin-dependent and requires a carboxyl-terminal dileucine motif
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DOI：
10.1074/jbc.m513154200
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发表时间：
2006-02-17
影响因子：
4.8
通讯作者：
Van der Westhuyzen, DR
中科院分区：
文献类型：
--
作者：
Eckhardt, ERM;Cai, L;Van der Westhuyzen, DR
高密度脂蛋白 (HDL) 受体清道夫受体 BII (SR-BII) 由 SR-BI 基因的选择性剪接 mRNA 编码，并在多种组织中表达。 SR-BII 蛋白与 SR-BI 的不同之处仅在于羧基末端胞质尾部，正如我们之前所表明的，该尾部必须包含赋予 HDL 主要细胞内表达和快速内吞作用的信号。我们已经证明 SR-BII 通过网格蛋白依赖性、小凹独立性途径介导 HDL 内吞作用。在尾部鉴定出两个候选氨基酸基序，可以介导与含有网格蛋白的内吞小泡的关联：在位置492-493处的推定双亮氨酸基序和在位置489处开始的基于酪氨酸的重叠YXXZ基序。虽然在位置489处用丙氨酸或组氨酸取代酪氨酸并不影响内吞作用，但取代L492A导致HDL表面结合增加并减少HDL颗粒内吞作用。替代品 L493A 的效果不那么显着。羧基末端尾部的其他区域似乎不包含 HDL 内吞作用所需的基序。 492位亮氨酸被疏水性氨基酸缬氨酸或苯丙氨酸取代也减少了HDL内吞作用，强调了该位置亮氨酸的重要性。将SR-BII YTPLL基序引入SR-BI的羧基末端胞质尾，将SR-BI转化为类似于SR-BII的内吞受体。这些结果表明，SR-BII 在亚细胞定位和运输方面与 SR-BI 不同，并表明这两种亚型在细胞内靶向配体的方式上有所不同。
The high density lipoprotein (HDL) receptor Scavenger Receptor BII (SR-BII) is encoded by an alternatively spliced mRNA from the SR-BI gene and is expressed in various tissues. SR-BII protein differs from SR-BI only in the carboxyl-terminal cytoplasmic tail, which, as we showed previously, must contain a signal that confers predominant intracellular expression and rapid endocytosis of HDL. We haveshown thatSR-BII mediates HDL endocytosis through a clathrin-dependent, caveolae-independent pathway. Two candidate amino acid motifs were identified in the tail that could mediate association with clathrin-containing endocytic vesicles: a putative dileucine motif at position 492-493 and an overlapping tyrosine-based YXXZ motif starting at position 489. Although substitution of tyrosine at position 489 with alanine or histidine did not affect endocytosis, substitution L492A resulted in increased surface binding of HDL and reduced HDL particle endocytosis. Substitution L493A had a less dramatic effect. No other regions in the carboxyl-terminal tail appeared to contain motifs required for HDL endocytosis. Substitutions of leucine at position 492 with the hydrophobic amino acids valine or phenylalanine also reduced HDL endocytosis, stressing the importance of leucine at this position. Introducing the SR-BII YTPLL motif into the carboxyl-terminal cytoplasmic tail of SR-BI converted SR-BI into an endocytic receptor resembling SR-BII. These results demonstrated that SR- BII differs from SR-BI in subcellular localization and trafficking and suggest that the two isoforms differ in the manner in which they target ligands intracellularly.