A PKC-dependent recruitment of MMP-2 controls semaphorin-3A growth-promoting effect in cortical dendrites.
There is increasing evidence for a crucial role of proteases and metalloproteinases during axon growth and guidance. In this context, we recently described a functional link between the chemoattractive Sema3C and Matrix metalloproteinase 3 (MMP3). Here, we provide data demonstrating the involvement of MMP-2 to trigger the growth-promoting effect of Sema3A in cortical dendrites. The in situ analysis of MMP-2 expression and activity is consistent with a functional growth assay demonstrating in vitro that the pharmacological inhibition of MMP-2 reduces the growth of cortical dendrites in response to Sema3A. Hence, our results suggest that the selective recruitment and activation of MMP-2 in response to Sema3A requires a PKC alpha dependent mechanism. Altogether, we provide a second set of data supporting MMPs as effectors of the growth-promoting effects of semaphorins, and we identify the potential signalling pathway involved.
INSERM U575, Physiopathologie du Système Nerveux, Strasbourg, France.
Bertrand
B
Gonthier
Eric
E
Koncina
Saulius
S
Satkauskas
Martine
M
Perraut
Guy
G
Roussel
Dominique
D
Aunis
Josef P
JP
Kapfhammer
Dominique
D
Bagnard
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002478:Cells, Cultured; D017931:DNA Primers; D003712:Dendrites; D007150:Immunohistochemistry; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000201:enzymology; D011480:Protease Inhibitors / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D040121:Semaphorin-3A / Q000502:physiology*; D015854:Up-Regulation
D017931:DNA Primers; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D040121:Semaphorin-3A; D011493:Protein Kinase C; D020778:Matrix Metalloproteinase 2