title: RET modulates cell adhesion via its cleavage by caspase in sympathetic neurons.
abstract: RET is a tyrosine kinase receptor involved in numerous cellular mechanisms including proliferation, neuronal navigation, migration, and differentiation upon binding with glial cell derived neurotrophic factor family ligands. RET is an atypical tyrosine kinase receptor containing four cadherin domains in its extracellular part. Furthermore, it has been shown to act as a dependence receptor. Such a receptor is active in the absence of ligand, triggering apoptosis through a mechanism that requires receptor intracellular caspase cleavage. However, different data suggest that RET is not always associated with the cell death/survival balance but rather provides positional information. We demonstrate here that caspase cleavage of RET is involved in the regulation of adhesion in sympathetic neurons. The cleavage of RET generates an N-terminal truncated fragment that functions as a cadherin accessory protein, modifying cadherin environment and potentiating cadherin-mediated cell aggregation. Thus, the caspase cleavage of RET generates two RET fragments: one intracellular domain that can trigger cell death in apoptotic permissive settings, and one membrane-anchored ectodomain with cadherin accessory activity. We propose that this latter function may notably be important for the adequate development of the superior cervical ganglion.
authors.affiliation: Apoptosis, Cancer, and Development Laboratory, Equipe labellisée La Ligue, Centre de Cancérologie de Lyon, INSERM U1052, CNRS UMR586, Université de Lyon, 69008 Lyon, France.
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Cabrera
authors.forename: Jimena
authors.initials: J
authors.lastname: Bouzas-Rodriguez
authors.forename: Servane
authors.initials: S
authors.lastname: Tauszig-Delamasure
authors.forename: Patrick
authors.initials: P
authors.lastname: Mehlen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D019556:COS Cells; D015820:Cadherins / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism; D002522:Chlorocebus aethiops; D005724:Ganglia / Q000378:metabolism; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D006801:Humans; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D051096:Proto-Oncogene Proteins c-ret / Q000378:metabolism* / Q000502:physiology*
chemical_list: D015820:Cadherins; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051096:Proto-Oncogene Proteins c-ret; D020169:Caspases