Regulation of BDNF Release by ARMS/Kidins220 through Modulation of Synaptotagmin-IV Levels

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Saray López-BenitoJuan C Arévalo

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 proper...Continue Reading

Citations

Jul 3, 2019·Brain Pathology·Álvaro Sebastián-SerranoTeresa Iglesias
Oct 21, 2019·Molecular Diagnosis & Therapy·Miao ZhaoXiang Lin
Oct 19, 2019·Cell Death and Differentiation·Fanny JaudonFabrizia Cesca
Sep 11, 2020·American Journal of Medical Genetics. Part a·Sara H El-DessoukyMaha Saad Zaki
Sep 9, 2020·Cell and Tissue Research·Masami KojimaTeiichi Furuichi
Sep 19, 2020·Cell and Tissue Research·Tanja Brigadski, Volkmar Leßmann
Feb 24, 2021·Cellular and Molecular Life Sciences : CMLS·Mónica C Quiñones-Frías, J Troy Littleton
May 19, 2021·Molecular Psychiatry·Ana Del PuertoTeresa Iglesias

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