Golgi Complex Dynamics and Its Implication in Prevalent Neurological Disorders

Caracci, Mario; Fuentealba, Luz M.; Marzolo, María‐Paz

doi:10.3389/fcell.2019.00075

Cited by 28 publications

(22 citation statements)

References 150 publications

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“…Accumulating evidences have established the functional involvement of golgins in neuronal excitability, polarity, migration and stress response addressing their contribution to neurological diseases. 21 – 23 …”

Section: Discussionmentioning

confidence: 99%

Chromosome 15q BP4-BP5 Deletion in a Girl with Nocturnal Frontal Lobe Epilepsy, Migraine, Circumscribed Hypertrichosis, and Language Impairment

et al. 2020

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The 15q13.3 microdeletion (microdel15q13.3) syndrome (OMIM 612001) has been reported in healthy subjects as well as in individuals with a wide spectrum of clinical manifestations ranging from mild to severe neurological disorders, including developmental delay/intellectual disability, autism spectrum disorder, schizophrenia, epilepsy, behavioral problems and speech dysfunction. This study explored the link between this genomic rearrangement and nocturnal frontal lobe epilepsy (NFLE), which could improve the clinical interpretation. A clinical and genomic investigation was carried out on an 8-year-girl with a de novo deletion flanking the breakpoints (BPs) 4 and 5 of 15q13.3 detected by array comparative genomic hybridization analysis, affected by NFLE, migraine with aura, minor facial features, mild cognitive and language impairment, and circumscribed hypertrichosis. Literature survey of clinical studies was included. Nine years follow-up have displayed a benign course of the epileptic disorder with a progressive reduction and disappearance of the epileptic seizures, mild improvement of cognitive and language skills, partial cutaneous hypertrichosis regression, but stable ongoing of migraine episodes. A likely relationship between the BP4–BP5 deletion and NFLE with other symptoms presented by the girl is discussed together with a review of the literature on phenotypic features in microdel15q13.3.

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Section: Discussionmentioning

confidence: 99%

Chromosome 15q BP4-BP5 Deletion in a Girl with Nocturnal Frontal Lobe Epilepsy, Migraine, Circumscribed Hypertrichosis, and Language Impairment

et al. 2020

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“…Finally, Golgi outposts have also been found to act as microtubule-organizing centers in dendrites, a role which is essential for the formation and maintenance of the dendritic arbor (Ori-McKenney et al, 2012;Yang and Wildonger, 2020). For excellent, recent reviews on the role of the secretory pathway in neurons and the role of the Golgi complex in neurological disorders see Kennedy and Hanus (2019) and Caracci et al (2019).…”

Section: Protein Synthesis and Trafficking In Development And Maintenmentioning

confidence: 99%

Homeostatic Roles of the Proteostasis Network in Dendrites

Lottes

Cox

2020

Front. Cell. Neurosci.

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Cellular protein homeostasis, or proteostasis, is indispensable to the survival and function of all cells. Distinct from other cell types, neurons are long-lived, exhibiting architecturally complex and diverse multipolar projection morphologies that can span great distances. These properties present unique demands on proteostatic machinery to dynamically regulate the neuronal proteome in both space and time. Proteostasis is regulated by a distributed network of cellular processes, the proteostasis network (PN), which ensures precise control of protein synthesis, native conformational folding and maintenance, and protein turnover and degradation, collectively safeguarding proteome integrity both under homeostatic conditions and in the contexts of cellular stress, aging, and disease. Dendrites are equipped with distributed cellular machinery for protein synthesis and turnover, including dendritically trafficked ribosomes, chaperones, and autophagosomes. The PN can be subdivided into an adaptive network of three major functional pathways that synergistically govern protein quality control through the action of (1) protein synthesis machinery; (2) maintenance mechanisms including molecular chaperones involved in protein folding; and (3) degradative pathways (e.g., Ubiquitin-Proteasome System (UPS), endolysosomal pathway, and autophagy. Perturbations in any of the three arms of proteostasis can have dramatic effects on neurons, especially on their dendrites, which require tightly controlled homeostasis for proper development and maintenance. Moreover, the critical importance of the PN as a cell surveillance system against protein dyshomeostasis has been highlighted by extensive work demonstrating that the aggregation and/or failure to clear aggregated proteins figures centrally in many neurological disorders. While these studies demonstrate the relevance of derangements in proteostasis to human neurological disease, here we mainly review recent literature on homeostatic developmental roles the PN machinery plays in the establishment, maintenance, and plasticity of stable and dynamic dendritic arbors. Beyond basic housekeeping functions, we consider roles of PN machinery in protein quality control mechanisms linked to dendritic plasticity (e.g., dendritic spine remodeling during LTP); cell-type specificity; dendritic morphogenesis; and dendritic pruning.

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“…Neuronal polarization is known to depend on the positioning of the Golgi apparatus, and thus, the biochemical mechanisms in that organelle should have important effects on this event (Villarroel-Campos et al, 2016 ; Tortosa and Hoogenraad, 2018 ; Caracci et al, 2019 ). Although such biochemical processes are not completely understood, one essential modification performed in the Golgi apparatus is protein palmitoylation, which regulates the trafficking of proteins for axon specification (Rodríguez-Asiain et al, 2011 ; Tortosa et al, 2017 ; Tortosa and Hoogenraad, 2018 ).…”

Section: Neuronal Polarization Related To Lipid Raftsmentioning

confidence: 99%

Neuronal Signaling Involved in Neuronal Polarization and Growth: Lipid Rafts and Phosphorylation

Igarashi

Honda

Kawasaki

et al. 2020

Front. Mol. Neurosci.

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Neuronal polarization and growth are developmental processes that occur during neuronal cell differentiation. The molecular signaling mechanisms involved in these events in in vivo mammalian brain remain unclear. Also, cellular events of the neuronal polarization process within a given neuron are thought to be constituted of many independent intracellular signal transduction pathways (the "tug-of-war" model). However, in vivo results suggest that such pathways should be cooperative with one another among a given group of neurons in a region of the brain. Lipid rafts, specific membrane domains with low fluidity, are candidates for the hotspots of such intracellular signaling. Among the signals reported to be involved in polarization, a number are thought to be present or translocated to the lipid rafts in response to extracellular signals. As part of our analysis, we discuss how such novel molecular mechanisms are combined for effective regulation of neuronal polarization and growth, focusing on the significance of the lipid rafts, including results based on recently introduced methods.

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Golgi Complex Dynamics and Its Implication in Prevalent Neurological Disorders

Cited by 28 publications

References 150 publications

Chromosome 15q BP4-BP5 Deletion in a Girl with Nocturnal Frontal Lobe Epilepsy, Migraine, Circumscribed Hypertrichosis, and Language Impairment

Chromosome 15q BP4-BP5 Deletion in a Girl with Nocturnal Frontal Lobe Epilepsy, Migraine, Circumscribed Hypertrichosis, and Language Impairment

Homeostatic Roles of the Proteostasis Network in Dendrites

Neuronal Signaling Involved in Neuronal Polarization and Growth: Lipid Rafts and Phosphorylation

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