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Title: Regulation of BDNF Release by ARMS/Kidins220 through Modulation of Synaptotagmin-IV Levels
Author: López Benito, Saray
Sánchez Sánchez, Julia
Brito, Verónica
Calvo, Laura
Lisa, Silvia
Torres Valle, María
Palko, Mary E.
Vicente García, Cristina
Fernández Fernández, Seila
Bolaños, Juan P.
Ginés Padrós, Silvia
Tessarollo, Lino
Arévalo, Juan C.
Keywords: Factors de creixement
Sistema nerviós central
Growth factors
Central nervous system
Issue Date: 16-May-2018
Publisher: The Society for Neuroscience
Abstract: BDNF is a growth factor with important roles in the nervous system in both physiological and pathological conditions, but the mechanisms controlling its secretion are not completely understood. Here, we show that ARMS/Kidins220 negatively regulates BDNF secretion in neurons from the CNS and PNS. Downregulation of the ARMS/Kidins220 protein in the adult mouse brain increases regulated BDNF secretion, leading to its accumulation in the striatum. Interestingly, two mouse models of Huntington's disease (HD) showed increased levels of ARMS/Kidins220 in the hippocampus and regulated BDNF secretion deficits. Importantly, reduction of ARMS/Kidins220 in hippocampal slices from HD mice reversed the impaired regulated BDNF release. Moreover, there are increased levels of ARMS/Kidins220 in the hippocampus and PFC of patients with HD. ARMS/Kidins220 regulates Synaptotagmin-IV levels, which has been previously observed to modulate BDNF secretion. These data indicate that ARMS/Kidins220 controls the regulated secretion of BDNF and might play a crucial role in the pathogenesis of HD.SIGNIFICANCE STATEMENT BDNF is an important growth factor that plays a fundamental role in the correct functioning of the CNS. The secretion of BDNF must be properly controlled to exert its functions, but the proteins regulating its release are not completely known. Using neuronal cultures and a new conditional mouse to modulate ARMS/Kidins220 protein, we report that ARMS/Kidins220 negatively regulates BDNF secretion. Moreover, ARMS/Kidins220 is overexpressed in two mouse models of Huntington's disease (HD), causing an impaired regulation of BDNF secretion. Furthermore, ARMS/Kidins220 levels are increased in brain samples from HD patients. Future studies should address whether ARMS/Kidins220 has any function on the pathophysiology of HD.
Note: Reproducció del document publicat a:
It is part of: Journal of Neuroscience, 2018, vol. 38, num. 23, p. 5415-5428
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ISSN: 0270-6474
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Biomedicina)

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