Abstract
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.
Highlights
Several families of guidance molecules including eph/ephrins [1,2], netrins [3], slits [4] and semaphorins [5,6] have been identified over the past ten years
Our results demonstrate that the growth promoting effect of Sema3A on cortical dendrites requires matrix metalloproteinases (MMPs)-2 by a mechanism of transduction implicating at least neuropilin-1 and a PKCa-dependent pathway
Sema3A has been described as a chemottractant for the dendrites of cortical neurons, a surprising effect in comparison to the inhibitory effect of Sema3A in axons [12]
Summary
Several families of guidance molecules including eph/ephrins [1,2], netrins [3], slits [4] and semaphorins [5,6] have been identified over the past ten years. The mechanisms initially described for axon guidance have been shown to control dendritic growth and guidance [8] consistently with the many roles described for semaphorins [9] This is the case for class 3 semaphorins which are key regulators of cortical wiring [10,11]. The chemorepulsive Sema3A was shown to reduce MMP-3 expression and activity consistently with its inhibitory effect on axons. Our results demonstrate that the growth promoting effect of Sema3A on cortical dendrites requires MMP-2 by a mechanism of transduction implicating at least neuropilin-1 and a PKCa-dependent pathway
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