title: Sorting protein-related receptor SorLA controls regulated secretion of glial cell line-derived neurotrophic factor.
abstract: 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.
authors: Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China.
authors: Zhao
authors: Z
authors: Geng
authors: Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China.
authors: Feng-Yi
authors: FY
authors: Xu
authors: Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China.
authors: Shu-Hong
authors: SH
authors: Huang
authors: Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China. Electronic address: zheyuchen@sdu.edu.cn.
authors: Zhe-Yu
authors: ZY
authors: Chen
mesh_terms: D000818:Animals; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D016716:PC12 Cells; D017434:Protein Structure, Tertiary; D051381:Rats; D022142:Secretory Vesicles / Q000235:genetics / Q000378:metabolism*
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D026502:LDL-Receptor Related Proteins; D026901:Membrane Transport Proteins; C102582:SORL1 protein, human