Organelle mapping in dendrites of human iPSC-derived neurons reveals dynamic functional dendritic Golgi structures

Wang, Jingqi; Daniszewski, Maciej; Hao, Marlene M; Hernández, Damián; Pébay, Alice; Gleeson, Paul A.; Fourrière, Lou

doi:10.1016/j.celrep.2023.112709

Cited by 11 publications

(4 citation statements)

References 54 publications

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“…Noteworthy, neurons from PSCs have somatic and dendritic Golgi structures and replicate the intrinsic Golgi dynamics within the dendritic compartments 55 and thus would provide an adequate environment for modeling intracellular 5-HT2ARs involved in psychedelic-induced plasticity. 11 Moreover, genome editing for endogenously regulated tagging is a promising approach that does not compromise PSCs’ pluripotency or differentiation potential, in which 5-HT2AR could be tagged and tracked within the neuronal progeny.…”

Section: What Do Psc-derived Brain Cells Bring To Psychedelic Studies?mentioning

confidence: 99%

Human pluripotent stem cells as a translational toolkit in psychedelic research in vitro

Salerno,

Rehen

2024

iScience

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Section: What Do Psc-derived Brain Cells Bring To Psychedelic Studies?mentioning

confidence: 99%

Human pluripotent stem cells as a translational toolkit in psychedelic research in vitro

Salerno,

Rehen

2024

iScience

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“…However, neurons have long axons and highly arborized dendrites, which complicate trafficking processes and demand on Rab7 function. In dendrites, distinct endosomal compartments are found in characteristic spatial distributions, with late endosomes more sparse distally and lysosomes overwhelmingly proximal [ 46 , 47 , 48 ]. Rab7 populates late endosomal/lysosomal compartments that are more degradative as they localize more proximally in the dendrite and the soma [ 46 , 49 , 50 ].…”

Section: Physiologic Control Of Rab7 In Neuronal Trafficking and Trop...mentioning

confidence: 99%

Regulation of Endosomal Trafficking by Rab7 and Its Effectors in Neurons: Clues from Charcot–Marie–Tooth 2B Disease

Mulligan,

Winckler

2023

Biomolecules

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Intracellular endosomal trafficking controls the balance between protein degradation and synthesis, i.e., proteostasis, but also many of the cellular signaling pathways that emanate from activated growth factor receptors after endocytosis. Endosomal trafficking, sorting, and motility are coordinated by the activity of small GTPases, including Rab proteins, whose function as molecular switches direct activity at endosomal membranes through effector proteins. Rab7 is particularly important in the coordination of the degradative functions of the pathway. Rab7 effectors control endosomal maturation and the properties of late endosomal and lysosomal compartments, such as coordination of recycling, motility, and fusion with downstream compartments. The spatiotemporal regulation of endosomal receptor trafficking is particularly challenging in neurons because of their enormous size, their distinct intracellular domains with unique requirements (dendrites vs. axons), and their long lifespans as postmitotic, differentiated cells. In Charcot–Marie–Tooth 2B disease (CMT2B), familial missense mutations in Rab7 cause alterations in GTPase cycling and trafficking, leading to an ulcero-mutilating peripheral neuropathy. The prevailing hypothesis to account for CMT2B pathologies is that CMT2B-associated Rab7 alleles alter endocytic trafficking of the neurotrophin NGF and its receptor TrkA and, thereby, disrupt normal trophic signaling in the peripheral nervous system, but other Rab7-dependent pathways are also impacted. Here, using TrkA as a prototypical endocytic cargo, we review physiologic Rab7 effector interactions and control in neurons. Since neurons are among the largest cells in the body, we place particular emphasis on the temporal and spatial regulation of endosomal sorting and trafficking in neuronal processes. We further discuss the current findings in CMT2B mutant Rab7 models, the impact of mutations on effector interactions or balance, and how this dysregulation may confer disease.

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“…Early research demonstrated the presence and function of ERES complexes in the dendrites (Horton and Ehlers, 2003;Aridor et al, 2004). Locally secreted cargoes can either traffic to the PM directly via an unconventional pathway or progress through Golgi outposts or satellites present in the dendrite (Mikhaylova et al, 2016;Kemal et al, 2022;Wang et al, 2023). The lack of complete Golgi machinery poses the possibility that unconventional secretion pathways could be an important mechanism of delivery.…”

Section: Local Translation and Secretion: Unconventional Pathways In ...mentioning

confidence: 99%

A voyage from the ER: spatiotemporal insights into polarized protein secretion in neurons

Kersten,

Farías

2023

Front. Cell Dev. Biol.

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To function properly, neurons must maintain a proteome that differs in their somatodendritic and axonal domain. This requires the polarized sorting of newly synthesized secretory and transmembrane proteins into different vesicle populations as they traverse the secretory pathway. Although the trans-Golgi-network is generally considered to be the main sorting hub, this sorting process may already begin at the ER and continue through the Golgi cisternae. At each step in the sorting process, specificity is conferred by adaptors, GTPases, tethers, and SNAREs. Besides this, local synthesis and unconventional protein secretion may contribute to the polarized proteome to enable rapid responses to stimuli. For some transmembrane proteins, some of the steps in the sorting process are well-studied. These will be highlighted here. The universal rules that govern polarized protein sorting remain unresolved, therefore we emphasize the need to approach this problem in an unbiased, top-down manner. Unraveling these rules will contribute to our understanding of neuronal development and function in health and disease.

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Organelle mapping in dendrites of human iPSC-derived neurons reveals dynamic functional dendritic Golgi structures

Cited by 11 publications

References 54 publications

Human pluripotent stem cells as a translational toolkit in psychedelic research in vitro

Human pluripotent stem cells as a translational toolkit in psychedelic research in vitro

Regulation of Endosomal Trafficking by Rab7 and Its Effectors in Neurons: Clues from Charcot–Marie–Tooth 2B Disease

A voyage from the ER: spatiotemporal insights into polarized protein secretion in neurons

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