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pubmed:abstractText |
Glial cell line-derived neurotrophic factor (GDNF) and a related factor, neurturin, promote survival of diverse groups of neurons. Both GDNF and neurturin signal via a two-component receptor complex that consists of a ligand-binding GDNF family receptor (GFRalpha-1 or GFRalpha-2) and the receptor protein tyrosine kinase Ret. Recently, a third receptor related to GFRalpha-1 and GFRalpha-2 has also been isolated and designated GFRalpha-3. Although much is known about the interaction among GDNF family factors, Ret, and the alpha-receptors in vitro, it remains unclear about their interactions in vivo. We show here by in situ hybridization that Ret and the alpha-receptors may be colocalized in the same tissues or expressed separately in projecting and target tissues, respectively, indicating that two distinct modes of interaction between Ret and the alpha-receptors exist in vivo. First, Ret may interact with the alpha-receptors expressed in the same cells (termed interaction "in cis") in many tissues and cell populations that respond to GDNF and/or neurturin, such as the substantia nigra, dorsal root ganglia, spinal cord motoneurons, kidney, and intestine. Second, Ret may interact with the alpha-receptors localized in the target neurons (termed interaction "in trans"). In addition, we present evidence in vitro that GFRalpha-1 mediates Ret activation by GDNF in trans. These observations suggest that there are multiple mechanisms regulating the interaction between Ret and the alpha-receptors that mediates the effects of GDNF family trophic factors on the survival and differentiation of cells and on neuron-target interactions in the nervous system.
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pubmed:affiliation |
Laboratory for Cancer Research, Department of Chemical Biology, College of Pharmacy, Rutgers University, Piscataway, New Jersey 08855, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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