GDNF isoform affects intracellular trafficking and secretion of GDNF in neuronal cells.
Glial cell line derived neurotrophic factor (GDNF) plays a critical role in central and peripheral neuron survival and function. In human and rodents, GDNF exists in an alternative spliced isoform (GDNF Delta 78), which has a 78 bp deletion in the pro-region of the GDNF encoding sequence. Whether the GDNF isoform affects GDNF function is unknown. Here, we investigated the secretion and intracellular localization of the GDNF Delta 78 isoform in neuronal cell populations. Our data indicate that a decreased secretion and an abnormal intracellular distribution of GDNF Delta 78 occurred in neuronal cells. The colocalization studies revealed much more localization of GDNF Delta 78 with Golgi marker-TGN38, which indicates that the accumulation of GDNF Delta 78 in the Golgi apparatus might in part account for its intracellular trafficking and secretion deficit. To our knowledge, it is reported for the first time that the GDNF Delta 78 isoform has a deficit in GDNF intracellular trafficking and secretion.
Wang
Yue
Y
Department of Neurobiology, School of Medicine, Shandong University, No.44 Wenhua Xi Road, Jinan, Shandong 250012, China.
Geng
Zhao
Z
Zhao
Ling
L
Huang
Shu-Hong
SH
Sheng
Ai-Li
AL
Chen
Zhe-Yu
ZY
D017398:Alternative Splicing; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004622:Embryo, Mammalian; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D008562:Membrane Glycoproteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D011247:Pregnancy; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection
D051100:Glial Cell Line-Derived Neurotrophic Factor; D008562:Membrane Glycoproteins; D020033:Protein Isoforms; C513045:Tgoln2 protein, rat