Artículo
Inhibition of L-Type Ca 2+ Channels by TRPC1-STIM1 Complex Is Essential for the Protection of Dopaminergic Neurons
Sun, Yuyang; Zhang, Haopeng; Selvaraj, Senthil; Sukumaran, Pramod; Lei, Saobo; Birnbaumer, Lutz
; Singh, Brij B.
Fecha de publicación:
03/2017
Editorial:
Society for Neuroscience
Revista:
Journal of Neuroscience
ISSN:
0270-6474
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Loss of dopaminergic (DA) neurons leads to Parkinson’s disease; however, the mechanism(s) for the vulnerability of DA neurons is(are) not fully understood. We demonstrate that TRPC1 regulates the L-type Ca2 channel that contributes to the rhythmic activity of adult DA neurons in the substantia nigra region. Store depletion that activates TRPC1, via STIM1, inhibits the frequency and amplitude of the rhythmic activity in DA neurons of wild-type, but not in TRPC1/, mice. Similarly, TRPC1/ substantia nigra neurons showed increased L-type Ca2 currents, decreased stimulation-dependent STIM1-Cav1.3 interaction, and decreased DA neurons. L-type Ca2 currents and the open channel probability of Cav1.3 channels were also reduced upon TRPC1 activation, whereas increased Cav1.3 currents were observed upon STIM1 or TRPC1 silencing. Increased interaction between Cav1.3-TRPC1-STIM1 was observed upon store depletion and the loss of either TRPC1 or STIM1 led to DA cell death, which was prevented by inhibiting L-type Ca2 channels. Neurotoxins that mimic Parkinson’s disease increased Cav1.3 function, decreased TRPC1 expression, inhibited Tg-mediated STIM1-Cav1.3 interaction, and induced caspase activation. Importantly, restoration of TRPC1 expression not only inhibited Cav1.3 function but increased cell survival. Together, we provide evidence that TRPC1 suppresses Cav1.3 activity by providing an STIM1-based scaffold, which is essential for DA neuron survival.
Palabras clave:
Calcium
,
Cav1.3
,
Parkinson’S Disease
,
Soce
,
Trpc1-Stim1
Archivos asociados
Licencia
Identificadores
Colecciones
Articulos(OCA HOUSSAY)
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Citación
Sun, Yuyang; Zhang, Haopeng; Selvaraj, Senthil; Sukumaran, Pramod; Lei, Saobo; et al.; Inhibition of L-Type Ca 2+ Channels by TRPC1-STIM1 Complex Is Essential for the Protection of Dopaminergic Neurons; Society for Neuroscience; Journal of Neuroscience; 37; 12; 3-2017; 3364-3377
Compartir
Altmétricas