Distribution of GDNF family receptor alpha 3 and RET in rat and human non-neural tissues

The neurotrophic growth factor artemin binds selectively to GDNF family receptor alpha 3 (GFR alpha 3), forming a molecular complex with the co-receptor RET which mediates downstream signaling. This signaling pathway has been demonstrated to play an important role in the survival and maintenance of nociceptive sensory neurons and in the development of sympathetic neurons. However, the presence and potential role of this artemin-responsive pathway in non-neural tissues has not been fully explored to-date. To study the distribution of GFR alpha 3 and RET in adult rat and human non-neural tissues, we carried out a comprehensive immunohistochemical study. We stained major organs from the digestive, urinary, reproductive, immune, respiratory and endocrine systems, and from other systems (cardiovascular, skeletal muscle), as well as regions of the nervous system for comparison. In both rat and human, the majority of non-neural cells did not exhibit detectable GFR alpha 3-like immunoreactivity. In the rat, GFR alpha 3- and RET-like staining were found in the same non-neural cell type only in kidney. In the human digestive and reproductive systems, a subset of epithelial cells exhibited GFR alpha 3- and RET-like staining, suggesting co-localization. In other tissues, sub-populations of cells expressed either GFR alpha 3- or RET-like immunoreactivity. The functional consequences of GFR alpha 3 expression in non-neural cells remain to be determined.