The role of microtubules in secretory protein transport

Fourrière, Lou; Jiménez, Ana Joaquina; Perez, Franck; Boncompain, Gaëlle

doi:10.1242/jcs.237016

Cited by 54 publications

(53 citation statements)

References 139 publications

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“…Many microtubule-dependent functions are exerted by microtubule-associated motors which are essential for microtubules to function as transport routes [67,68]. At the same time, motor proteins contribute to microtubule network organization by moving or sliding microtubules along each other [69,70].…”

Section: Control Of Microtubule Functionmentioning

confidence: 99%

Microtubule Organization in Striated Muscle Cells

Becker

Leone

Engel

2020

Cells

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Distinctly organized microtubule networks contribute to the function of differentiated cell types such as neurons, epithelial cells, skeletal myotubes, and cardiomyocytes. In striated (i.e., skeletal and cardiac) muscle cells, the nuclear envelope acts as the dominant microtubule-organizing center (MTOC) and the function of the centrosome—the canonical MTOC of mammalian cells—is attenuated, a common feature of differentiated cell types. We summarize the mechanisms known to underlie MTOC formation at the nuclear envelope, discuss the significance of the nuclear envelope MTOC for muscle function and cell cycle progression, and outline potential mechanisms of centrosome attenuation.

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Section: Control Of Microtubule Functionmentioning

confidence: 99%

Microtubule Organization in Striated Muscle Cells

Becker

Leone

Engel

2020

Cells

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“…Cytoskeletal elements, such as microtubules or actin filaments, play a pivotal role in regulating peptide hormone trafficking and secretion in endocrine cells (Rudolf et al, 2001;Park and Loh, 2008;Fourriere et al, 2020). In pancreatic islet β cells, for example, insulin secretion induced upon elevated levels of blood glucose is accompanied by increased polymerization of tubulin (Pipeleers et al, 1976;McDaniel et al, 1980;Heaslip et al, 2014) and a loosening of cortical F-actin (Kalwat and Thurmond, 2013).…”

Section: Introductionmentioning

confidence: 99%

3D FIB-SEM reconstruction of microtubule–organelle interaction in whole primary mouse β cells

Müller

Schmidt

et al. 2020

Journal of Cell Biology

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Microtubules play a major role in intracellular trafficking of vesicles in endocrine cells. Detailed knowledge of microtubule organization and their relation to other cell constituents is crucial for understanding cell function. However, their role in insulin transport and secretion is under debate. Here, we use FIB-SEM to image islet β cells in their entirety with unprecedented resolution. We reconstruct mitochondria, Golgi apparati, centrioles, insulin secretory granules, and microtubules of seven β cells, and generate a comprehensive spatial map of microtubule–organelle interactions. We find that microtubules form nonradial networks that are predominantly not connected to either centrioles or endomembranes. Microtubule number and length, but not microtubule polymer density, vary with glucose stimulation. Furthermore, insulin secretory granules are enriched near the plasma membrane, where they associate with microtubules. In summary, we provide the first 3D reconstructions of complete microtubule networks in primary mammalian cells together with evidence regarding their importance for insulin secretory granule positioning and thus their supportive role in insulin secretion.

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“… 71 In this respect, it is important to emphasize that the activation of ARF1 by GBF1 is crucial for the assembly of the COPI vesicle-coat complex at the Golgi and ERGIC membranes and that the inactivation or depletion of GBF1 causes COPI dissociation from membranes with concomitant GA fragmentation. 32 , 53 , 72 …”

Section: Main Textmentioning

confidence: 99%

De Novo and Inherited Variants in GBF1 are Associated with Axonal Neuropathy Caused by Golgi Fragmentation

Mendoza-Ferreira

Karakaya

Cengiz

et al. 2020

The American Journal of Human Genetics

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Distal hereditary motor neuropathies (HMNs) and axonal Charcot-Marie-Tooth neuropathy (CMT2) are clinically and genetically heterogeneous diseases characterized primarily by motor neuron degeneration and distal weakness. The genetic cause for about half of the individuals affected by HMN/CMT2 remains unknown. Here, we report the identification of pathogenic variants in GBF1 (Golgi brefeldin A-resistant guanine nucleotide exchange factor 1) in four unrelated families with individuals affected by sporadic or dominant HMN/CMT2. Genomic sequencing analyses in seven affected individuals uncovered four distinct heterozygous GBF1 variants, two of which occurred de novo . Other known HMN/CMT2-implicated genes were excluded. Affected individuals show HMN/CMT2 with slowly progressive distal muscle weakness and musculoskeletal deformities. Electrophysiological studies confirmed axonal damage with chronic neurogenic changes. Three individuals had additional distal sensory loss. GBF1 encodes a guanine-nucleotide exchange factor that facilitates the activation of members of the ARF (ADP-ribosylation factor) family of small GTPases. GBF1 is mainly involved in the formation of coatomer protein complex (COPI) vesicles, maintenance and function of the Golgi apparatus, and mitochondria migration and positioning. We demonstrate that GBF1 is present in mouse spinal cord and muscle tissues and is particularly abundant in neuropathologically relevant sites, such as the motor neuron and the growth cone. Consistent with the described role of GBF1 in Golgi function and maintenance, we observed marked increase in Golgi fragmentation in primary fibroblasts derived from all affected individuals in this study. Our results not only reinforce the existing link between Golgi fragmentation and neurodegeneration but also demonstrate that pathogenic variants in GBF1 are associated with HMN/CMT2.

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The role of microtubules in secretory protein transport

Cited by 54 publications

References 139 publications

Microtubule Organization in Striated Muscle Cells

Microtubule Organization in Striated Muscle Cells

3D FIB-SEM reconstruction of microtubule–organelle interaction in whole primary mouse β cells

De Novo and Inherited Variants in GBF1 are Associated with Axonal Neuropathy Caused by Golgi Fragmentation

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