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.