Nervous system development relies on endosomal trafficking

Abstract

Accumulating findings have begun to unveil the important role of the endosomal machinery in the nervous system development. Endosomes have been linked to the differential segregation of cell fate determining molecules in asymmetrically dividing progenitors during neurogenesis. Additionally, the precise removal and reinsertion of membrane components through endocytic trafficking regulates the spatial and temporal distribution of signaling receptors and adhesion molecules, which determine the morphology and motility of migrating neurons. Emerging evidence suggests that the role of the endosomal sorting adaptors is dependent upon cell type and developmental stage. The repertoire of the signaling receptors and/or adhesion molecules sorted by the endosome during these processes remains to be explored. In this commentary, we will briefly address the progress in this research field.KEYWORDS asymmetric mitosis; brain development; endosomal system; membrane trafficking; neuron migration; smad anchor for receptor activation (SARA)

Overlapping spectrums: The clinicogenetic commonalities between Charcot-Marie-Tooth and other neurodegenerative diseases

“…Endo-Lysosomal sorting and trafficking as well as axonal transport are both critical for axon growth, maintenance, and signaling (Cosker and Segal, 2014;Maday et al, 2014;Kalani and Tyagi, 2015;Mestres and Sung, 2017), so it is not surprising that mutations in the various genes associated with these processes have been tied to a wide variety of neurodegenerative diseases (De Vos et al, 2008;Hinckelmann et al, 2013;Millecamps and Julien, 2013;Neefjes and van der Kant, 2014;Prior et al, 2017;Burk and Pasterkamp, 2019;Vagnozzi and Praticò, 2019). In this section, we will take a closer look at a few of these genes that encode for proteins that make up the axon cytoskeleton, molecular motors, and vesicle trafficking and are implicated in a range of neuropathies (Fig.…”

Smad anchor for receptor activation nuclear localization during development identifies Layers V and VI of the neocortex

“…Accordingly, we have previously reported a punctate vesicle‐like distribution of endogenous SARA in the mice embryonic neocortex (Mestres, Chuang, Calegari, Conde, & Sung, ). We have also addressed its role in controlling membrane and membrane proteins trafficking and how this function is important for normal development of the nervous system (Mestres & Sung, ). Particularly, during neocortical development, SARA fine‐tunes the amount of the cell adhesion protein L1 that distributes to the cell surface of migrating neurons (Mestres et al, ).…”

Implicações de variantes bialélicas de perda de função no gene TBCK, no transporte de vesículas de células progenitoras neurais derivadas de células-tronco pluripotentes induzidas

“…Notch ativa e, portanto, a identidade de célula proliferativa. Em contrapartida, a degradação dos receptores nos lisossomos suprimem a atividade da via de sinalização Notch, induzindo a diferenciação das células progenitoras neurais em neurônios (Mestres et al, 2017;Shao et al, 2017). Utilizando-se desse tipo de estratégia, ou seja, a dinâmica remoção e (re)inserção ou degradação espaço-temporal de moléculas sinalizadoras em resposta aos estímulos celulares, a maquinaria do transporte de vesículas também coordena, de forma bastante sofisticada, as vias de sinalização que regulam outros processos neurodesenvolvimentais, como a migração neuronal, neuritogênese, e ainda o crescimento e direcionamento axonal (Winkle & Gupton, 2016;Yadaw et al, 2019).…”