Role of protein kinase d in Golgi exit and lysosomal targeting of the transmembrane protein, Mcoln1.
Role of protein kinase d in Golgi exit and lysosomal targeting of the transmembrane protein, Mcoln1.
复制标题
蛋白激酶 d 在高尔基体出口和跨膜蛋白 Mcoln1 的溶酶体靶向中的作用。
DOI：
10.1111/j.1600-0854.2012.01331.x
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Pagano,RichardE
中科院分区：
文献类型：
--
作者：
Marks,DavidL;Holicky,EileenL;Wheatley,ChristineL;Frumkin,Ayala;Bach,Gideon;Pagano,RichardE
The targeting of lysosomal transmembrane (TM) proteins from the Golgi apparatus to lysosomes is a complex process that is only beginning to be understood. Here, the lysosomal targeting of mucolipin‐1 (Mcoln1), the TM protein defective in the autosomal recessive disease, mucolipidosis type IV, was studied by overexpressing full‐length and truncated forms of the protein in human cells, followed by detection using immunofluorescence and immunoblotting. We demonstrated that a 53‐amino acid C‐terminal region of Mcoln1 is required for efficient exit from the Golgi. Truncations lacking this region exhibited reduced delivery to lysosomes and decreased proteolytic cleavage of Mcoln1 into characteristic ∼35‐kDa fragments, suggesting that this cleavage occurs in lysosomes. In addition, we found that the co‐expression of full‐length Mcoln1 with kinase‐inactive protein kinase D(PKD) 1 or 2 inhibited Mcoln1 Golgi exit and transport to lysosomes and decreased Mcoln1 cleavage. These studies suggest that PKDs play a role in the delivery of some lysosomal resident TM proteins from the Golgi to the lysosomes.
