Neural expression of sorting nexin 25 and its regulation of tyrosine receptor kinase B trafficking
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ORIGINAL ARTICLE
Neural expression of sorting nexin 25 and its regulation of tyrosine receptor kinase B trafficking Shoko Takemura1 · Ayami Isonishi1,2 · Tatsuhide Tanaka1 · Hiroaki Okuda1,3 · Kouko Tatsumi1 · Mariko Yamano1 · Akio Wanaka1 Received: 8 April 2020 / Accepted: 8 September 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Sorting nexin 25 (SNX25) belongs to the sorting nexin superfamily, whose members are responsible for membrane attachment to organelles of the endocytic system. Recent reports point to critical roles for SNX25 as a negative regulator of transforming growth factor β signaling, but the expression patterns of SNX25 in the central nervous system (CNS) remain almost uncharacterized. Here, we show widespread neuronal expression of SNX25 protein and Snx25 mRNA using immunohistochemistry and in situ hybridization. As an exception, SNX25 was present in the Bergmann glia of the cerebellum. SNX25 immunoreactivity was found in cholinergic and catecholaminergic neurons. Moreover, SNX25 colocalized with tropomyosin receptor kinase B (TrkB) in the neurons of the cortex and hippocampus. In vitro, SNX25 can interact with full-length TrkB, but not with its C-terminal-truncated isoform. Overexpression of SNX25 accelerated degradation of full-lengh TrkB, indicating that SNX25 promotes the trafficking of TrkB for lysosomal degradation. These findings suggest that SNX25 is a new actor in endocytic signaling, perhaps contributing to the regulation of BDNF–TrkB signaling in the CNS. Keyword BDNF · Cortex · Endosomal trafficking · Hippocampus · Lysosomal degradation Abbreviations III Oculomotor nucleus IV Trochlear nucleus V Motor nucleus of trigeminal VI Abducens nucleus VII Facial motor nucleus XII Hypoglossal nucleus AAA Anterior amygdalar area ACA Anterior cingulate area ACB Nucleus accumbens ACVII Accessory facial motor nucleus AD Anterodorsal nucleus ADP Anterodorsal preoptic nucleus * Shoko Takemura shtakemur@naramed‑u.ac.jp 1
Department of Anatomy and Neuroscience, Faculty of Medicine, Nara Medical University, 840 Shijo‑cho, Kashihara, Nara 634‑8521, Japan
2
Center for Diversity and Inclusion, Nara Medical University, 840 Shijo‑cho, Kashihara, Nara 634‑8521, Japan
3
Department of Functional Anatomy, Graduate School of Medical Sciences, Kanazawa University, 13‑1 Takara‑machi, Kanazawa, Ishikawa 920‑0934, Japan
AHN Anterior hypothalamic nucleus AI Agranular insular area AM Anteromedial nucleus AMB Nucleus ambiguus AOB Accessory olfactory bulb AON Anterior olfactory nucleus AP Area postrema ARH Arcuate hypothalamic nucleus AT Anterior tegmental nucleus AUD Auditory areas AV Anteroventral nucleus of thalamus AVP Anteroventral preoptic nucleus AVPV Anteroventral periventricular nucleus B Barrington’s nucleus BA Bed nucleus of the accessory olfactory tract BAC Bed nucleus of the anterior commissure BDNF Brain-derived neurotrophic factor BLA Basolateral amygdalar nucleus BMA Basomedial amygdalar nucleus BST Bed nuclei of the stria
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