Bidirectional regulation of neurite elaboration by alternatively spliced metabotropic glutamate receptor 5 (mGluR5) isoforms.
Alternative splicing in the mGluR5 gene generates two different receptor isoforms, of which expression is developmentally regulated. However, little is known about the functional significance of mGluR5 splice variants. We have examined the functional coupling, subcellular targeting, and effect on neuronal differentiation of epitope-tagged mGluR5 isoforms by expression in neuroblastoma NG108-15 cells. We found that both mGluR5 splice variants give rise to comparable [Ca2+]i transients and have similar pharmacological profile. Tagged receptors were shown by immunofluorescence to be inserted in the plasma membrane. In undifferentiated cells the subcellular localization of the two mGluR5 isoforms was partially segregated, whereas in differentiated cells the labeling largely redistributed to the newly formed neurites. Interestingly, we demonstrate that mGluR5 splice variants dramatically influence the formation and maturation of neurites; mGluR5a hinders the acquisition of mature neuronal traits and mGluR5b fosters the elaboration and extension of neurites. These effects are partly inhibited by MPEP.
Mion
S
S
Department of Medicine and Public Health, Pharmacology Section, Universita' di Verona, Policlinico Borgo Roma, Verona, 37134, Italy.
Corti
C
C
Neki
A
A
Shigemoto
R
R
Corsi
M
M
Fumagalli
G
G
Ferraguti
F
F
D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology; D002451:Cell Compartmentation / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics*; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D000939:Epitopes / Q000235:genetics / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D007150:Immunohistochemistry; D007425:Intracellular Membranes / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D016501:Neurites / Q000378:metabolism* / Q000648:ultrastructure; D009447:Neuroblastoma; D015388:Organelles / Q000378:metabolism / Q000648:ultrastructure; D020033:Protein Isoforms / Q000235:genetics*; D051381:Rats; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D000906:Antibodies; D000939:Epitopes; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; C578936:Grm5 protein, mouse; C578937:Grm5 protein, rat; D020033:Protein Isoforms; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D018698:Glutamic Acid; D001920:Bradykinin; D002118:Calcium