title: Activated somatostatin type 2 receptors traffic in vivo in central neurons from dendrites to the trans Golgi before recycling.
abstract: Understanding the trafficking of G-protein-coupled receptors (GPCRs) is of particular importance, especially when modifications of the neurochemic environment occur as in pathological or therapeutic circumstances. In the central nervous system, although some GPCRs were reported to internalize in vivo, little is known about their trafficking downstream of the endocytic event. To address this issue, distribution and expression pattern of the major somatostatin receptor subtype, the somatostatin type 2 (sst2), was monitored in the hippocampus using immunofluorescence, autoradiographic and immunogold experiments from 10 minutes to 7 days after in vivo injection of the receptor agonist octreotide. We then analyzed whether postendocytic trafficking of the receptor was dependent upon integrity of the microtubule network using colchicine-injected animals. Together, our results suggest that upon agonist stimulation, dendritic receptors are retrogradely transported through a microtubule-dependent mechanism to a trans Golgi domain enriched in the t-SNARE syntaxin 6 and trans Golgi network 38 proteins, before recycling. Because we show that the exit rate from the trans Golgi apparatus back to the plasma membrane (hours) is slower than the entry rate (minutes), the neuronal postendocytic trafficking of sst2 receptor is likely to have functional consequences in several neurological diseases in which an increase in somatostatin release occurs.
authors.affiliation: Neuroendocrine Research Laboratory, Department of Human Morphology and Developmental Biology, Hungarian Academy of Sciences and Semmelweis University, 1094 Budapest, Hungary.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Csaba
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lelouvier
authors.forename: Cécile
authors.initials: C
authors.lastname: Viollet
authors.forename: Vincent
authors.initials: V
authors.lastname: El Ghouzzi
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Toyama
authors.forename: Catherine
authors.initials: C
authors.lastname: Videau
authors.forename: Véronique
authors.initials: V
authors.lastname: Bernard
authors.forename: Pascal
authors.initials: P
authors.lastname: Dournaud
mesh_terms: D000818:Animals; D003712:Dendrites / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008870:Microtubules / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D050765:Qa-SNARE Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000378:metabolism*; D050600:SNARE Proteins / Q000378:metabolism; D021601:trans-Golgi Network / Q000378:metabolism
chemical_list: D050765:Qa-SNARE Proteins; D043562:Receptors, G-Protein-Coupled; D017481:Receptors, Somatostatin; D050600:SNARE Proteins; C093733:somatostatin receptor 2