标题：Sorting protein-related receptor SorLA controls regulated secretion of glial cell line-derived neurotrophic factor.
作者：Geng Z;Xu FY;Huang SH;Chen ZY
作者机构：[Geng, Z] Dept. of Neurobiology, School of Medicine, Shandong University, No.44 Wenhua Xi Rd, Jinan, Shandong 250012, China;[ Xu, F.-Y] Dept. of Neuro 更多
通讯作者地址：[Chen, ZY]Shandong Univ, Dept Neurobiol, Sch Med, Shandong Prov Key Lab Mental Disorders, 44 Wenhua Xi Rd, Jinan 250012, Shandong, Peoples R China.
来源：The Journal of biological chemistry
摘要：Glial cell line-derived neurotrophic factor (GDNF), after secreted from cells, plays a critical role in central and peripheral neuron survival and function. The secretion of GDNF can be either constitutive or regulated by physiological stimuli; however, the detailed mechanism driving GDNF secretion is still unknown. Here, we report that sorting protein-related receptor with A-type repeats (SorLA), a member of the mammal Vps10p domain receptor, interacts with GDNF and is localized to GDNF-containing vesicles. Overexpression of SorLA significantly increases, and knockdown of SorLA by siRNA decreases, the regulated secretion of GDNF in PC12 and MN9D cells but has no effect on GDNF constitutive secretion. In addition, overexpression of a truncated form of SorLA also impairs GDNF-regulated secretion. Finally, we found that the prodomain of GDNF mediates the interaction of GDNF with SorLA under acidic conditions. Moreover, overexpression of SorLA could enhance the regulated secretion of the GDNF prodomain-GFP fusion protein, suggesting that the prodomain of GDNF is responsible for its regulated secretion. Together, these findings will advance our understanding of the molecular mechanism underlying GDNF-regulated secretion.