Peer-Reviewed Journal Details
Mandatory Fields
Hegarty, S.V., Sullivan, A.M., O’Keeffe, G.W.
2017
February
Neuroscience Letters
Endocytosis contributes to BMP2-induced Smad signalling and neuronal growth
Published
Optional Fields
BMP(s) Bone morphogenetic protein(s) BMPR(s) BMP receptor(s) DA Dopaminergic DIV Day(s) in vitro PD Parkinson’s disease VM Ventral midbrain Endocytosis BMP2 Dynamin-dependent Smad signalling Neurite growth
643
32
37
Bone morphogenetic protein 2 (BMP2) is a neurotrophic factor which induces the growth of midbrain dopaminergic (DA) neurons in vitro and in vivo, and its neurotrophic effects have been shown to be dependent on activation of BMP receptors (BMPRs) and Smad 1/5/8 signalling. However, the precise intracellular cascades that regulate BMP2-BMPR-Smad-signalling-induced neurite growth remain unknown. Endocytosis has been shown to regulate Smad 1/5/8 signalling and differentiation induced by BMPs. However, these studies were carried out in non-neural cells. Indeed, there are scant reports regarding the role of endocytosis in BMP-Smad signalling in neurons. To address this, and to further characterise the mechanisms regulating the neurotrophic effects of BMP2, the present study examined the role of dynamin-dependent endocytosis in BMP2-induced Smad signalling and neurite growth in the SH-SY5Y neuronal cell line. The activation, temporal kinetics and magnitude of Smad 1/5/8 signalling induced by BMP2 were significantly attenuated by dynasore-mediated inhibition of endocytosis in SH-SY5Y cells. Furthermore, BMP2-induced increases in neurite length and neurite branching in SH-SY5Y cells were significantly reduced following inhibition of dynamin-dependent endocytosis using dynasore. This study demonstrates that BMP2-induced Smad signalling and neurite growth is regulated by dynamin-dependent endocytosis in a model of human midbrain dopaminergic neurons.
0304-3940
http://www.sciencedirect.com/science/article/pii/S0304394017301192
10.1016/j.neulet.2017.02.013
Grant Details
Science Foundation Ireland
15/CDA/13498