TY - JOUR
T1 - PLCγ-activated signalling is essential for TrkB mediated sensory neuron structural plasticity
AU - Sciarretta, Carla
AU - Fritzsch, Bernd
AU - Beisel, Kirk
AU - Rocha-Sanchez, Sonia M.
AU - Buniello, Annalisa
AU - Horn, Jacqueline M.
AU - Minichiello, Liliana
N1 - Funding Information:
The Authors would like to thank Emerald Perlas for technical assistance. This work was supported in part by a grant from the NIH/NIDCD (RO1DC005590) to BF, and a grant from the NIH/NIDCD (RO1DC009418) to LM.
PY - 2010
Y1 - 2010
N2 - Background. The vestibular system provides the primary input of our sense of balance and spatial orientation. Dysfunction of the vestibular system can severely affect a person's quality of life. Therefore, understanding the molecular basis of vestibular neuron survival, maintenance, and innervation of the target sensory epithelia is fundamental. Results. Here we report that a point mutation at the phospholipase C (PLC) docking site in the mouse neurotrophin tyrosine kinase receptor TrkB (Ntrk2) specifically impairs fiber guidance inside the vestibular sensory epithelia, but has limited effects on the survival of vestibular sensory neurons and growth of afferent processes toward the sensory epithelia. We also show that expression of the TRPC3 cation calcium channel, whose activity is known to be required for nerve-growth cone guidance induced by brain-derived neurotrophic factor (BDNF), is altered in these animals. In addition, we find that absence of the PLC mediated TrkB signalling interferes with the transformation of bouton type afferent terminals of vestibular dendrites into calyces (the largest synaptic contact of dendrites known in the mammalian nervous system) on type I vestibular hair cells; the latter are normally distributed in these mutants as revealed by an unaltered expression pattern of the potassium channel KCNQ4 in these cells. Conclusions. These results demonstrate a crucial involvement of the TrkB/PLC-mediated intracellular signalling in structural aspects of sensory neuron plasticity.
AB - Background. The vestibular system provides the primary input of our sense of balance and spatial orientation. Dysfunction of the vestibular system can severely affect a person's quality of life. Therefore, understanding the molecular basis of vestibular neuron survival, maintenance, and innervation of the target sensory epithelia is fundamental. Results. Here we report that a point mutation at the phospholipase C (PLC) docking site in the mouse neurotrophin tyrosine kinase receptor TrkB (Ntrk2) specifically impairs fiber guidance inside the vestibular sensory epithelia, but has limited effects on the survival of vestibular sensory neurons and growth of afferent processes toward the sensory epithelia. We also show that expression of the TRPC3 cation calcium channel, whose activity is known to be required for nerve-growth cone guidance induced by brain-derived neurotrophic factor (BDNF), is altered in these animals. In addition, we find that absence of the PLC mediated TrkB signalling interferes with the transformation of bouton type afferent terminals of vestibular dendrites into calyces (the largest synaptic contact of dendrites known in the mammalian nervous system) on type I vestibular hair cells; the latter are normally distributed in these mutants as revealed by an unaltered expression pattern of the potassium channel KCNQ4 in these cells. Conclusions. These results demonstrate a crucial involvement of the TrkB/PLC-mediated intracellular signalling in structural aspects of sensory neuron plasticity.
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U2 - 10.1186/1471-213X-10-103
DO - 10.1186/1471-213X-10-103
M3 - Article
C2 - 20932311
AN - SCOPUS:77957582056
VL - 10
JO - BMC Developmental Biology
JF - BMC Developmental Biology
SN - 1471-213X
M1 - 103
ER -