RAB6 and microtubules restrict protein secretion to focal adhesions

Fourrière, Lou; Kasri, Amal; Gareil, Nelly; Bardin, Sabine; Bousquet, Hugo; Pereira, David; Perez, Franck; Goud, Bruno; Boncompain, Gaëlle; Miserey-Lenkei, Stéphanie

doi:10.1083/jcb.201805002

Cited by 91 publications

(140 citation statements)

References 41 publications

(84 reference statements)

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“…Rab6, a small GTPase interacting with BICD2, is an established regulator of the secretory pathway (Grigoriev et al, 2007;Fourriere et al, 2019) and controls the flow of secreted proteins that are transported from the Golgi to the plasma membrane via a microtubule-dependent process. As a consequence, loss of Rab6 results in a global reduction of protein secretion (Bardin et al, 2015).…”

Section: Patient Fibroblasts Show Evidence Of Impaired Secretionmentioning

confidence: 99%

Loss of BICD2 in muscle drives motor neuron loss in a developmental form of spinal muscular atrophy

Rossor

Sleigh

Groves

et al. 2019

Preprint

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Running title: BICD2 ablation in muscle causes motor neuron loss Characters (excluding spaces): 18,564 Summary Missense mutations in the cargo adaptor protein BICD2 cause SMALED2, a developmental disease of motor neurons. In this study, the authors show that BICD2 mutations cause motor neuron loss by a non-cell autonomous mechanism determining a disabling impairment of muscle function.3 Abstract BICD2 is a key component of the dynein/dynactin motor complex. Autosomal dominant mutations in BICD2 cause Spinal Muscular Atrophy Lower Extremity Predominant 2 (SMALED2), a developmental disease of motor neurons. In this study we sought to examine the motor neuron phenotype of conditional Bicd2 -/mice. Bicd2 -/mice show a significant reduction in the number of motor axons of the L4 ventral root compared to wild type mice. Muscle-specific knockout of Bicd2, but not motor neuronspecific Bicd2 loss, results in a reduction in L4 ventral axons comparable to global Bicd2 -/mice. Rab6, a small GTPase required for the sorting of secretory vesicles from the TGN to the plasma membrane is a major binding partner of BICD2. We therefore examined the secretory pathway in SMALED2 patient fibroblasts and demonstrated impaired flow of constitutive secretory cargoes. Together, these data indicate that BICD2 loss from muscles is a major driver of non-cell autonomous pathology with important implications for future therapeutic approaches to SMALED2.

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Section: Patient Fibroblasts Show Evidence Of Impaired Secretionmentioning

confidence: 99%

Loss of BICD2 in muscle drives motor neuron loss in a developmental form of spinal muscular atrophy

Rossor

Sleigh

Groves

et al. 2019

Preprint

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“…Post-Golgi carriers have also been observed using the "retention using selective hooks" (RUSH) system [59,117]. By fusing a protein of interest to streptavidin-binding peptide (SBP) and coexpressing an ER localised streptavidin, RUSH allows the protein of interest to accumulate in the ER due to the interaction between the streptavidin and the SBP [118].…”

Section: Biosynthetic Lamp1 Carriersmentioning

confidence: 99%

“…Rab6 secretory carriers transport a large variety of cargos. Using the RUSH system, it was shown that Rab6 secretory carriers contain the anterograde cargos CD59, TNFα, and ColX and Rab6 depletion delays the delivery of these cargo to the plasma membrane [117]. Furthermore, Rab6 depletion in embryonic fibroblast cells reduces global protein secretion by 50%.…”

Section: Rab6 Associated Carriersmentioning

confidence: 99%

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Direct trafficking pathways from the Golgi apparatus to the plasma membrane

Stalder

Gershlick

2020

Seminars in Cell & Developmental Biology

100

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In eukaryotic cells, protein sorting is a highly regulated mechanism important for many physiological events. After synthesis in the endoplasmic reticulum and trafficking to the Golgi apparatus, proteins sort to many different cellular destinations including the endolysosomal system and the extracellular space. Secreted proteins need to be delivered directly to the cell surface. Sorting of secreted proteins from the Golgi apparatus has been a topic of interest for over thirty years, yet there is still no clear understanding of the machinery that forms the post-Golgi carriers. Most evidence points to these post-Golgi carriers being tubular pleomorphic structures that bud from the trans-face of the Golgi. In this review, we present the background studies and highlight the key components of this pathway, we then discuss the machinery implicated in the formation of these carriers, their translocation across the cytosol, and their fusion at the plasma membrane.Abbreviations: ATP, adenosine triphosphate; BFA, Brefeldin A; CARTS, CARriers of the TGN to the cell Surface; CI-MPR, cation-independent mannose-6 phosphate receptor; CtBP3/BARS, C-terminus binding protein 3/BFA adenosine diphosphate-ribosylated substrate; ER, endoplasmic reticulum; GlcCer, glucosylceramide; PAUF, pancreatic adenocarcinoma up-regulated factor; PM, plasma membrane; RUSH, retention using selective hooks; SBP, streptavidin-binding peptide; SM, sphingomyelin; SNARE, soluble N-ethylmaleimide sensitive fusion protein attachment protein receptor;SPCA1, secretory pathway calcium ATPase 1; TGN, trans-Golgi Network; TIRF, total internal reflection fluorescence; ts, temperature sensitive; VSV, vesicular stomatitis virus J o u r n a l P r e -p r o o f J o u r n a l P r e -p r o o f J o u r n a l P r e -p r o o f J o u r n a l P r e -p r o o f

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“…Microtubules are nucleated at microtubule organizing centers, often the centrosomes, and elongate through sequential phases of growth and shortening, until reaching structures, such as the cell cortex or kinetochores, where they will be captured and stabilized. Microtubule stabilization at the cell cortex is required for oriented trafficking of intracellular vesicles and directed cell motility [1][2][3] . Astral microtubule capture during mitosis is required for mitotic spindle orientation and positioning of the mitotic spindle.…”

Section: Introductionmentioning

confidence: 99%

iASPP contributes to cortex rigidity, astral microtubule capture and mitotic spindle positioning

Mangon

Salaün

Bouali

et al. 2019

Preprint

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The microtubule plus-end binding protein EB1 is the core of a complex protein network which regulates microtubule dynamics during important biological processes such as cell motility and mitosis. We found that iASPP, an inhibitor of p53 and predicted regulatory subunit of the PP1 phosphatase, associates with EB1 at microtubule plus-ends via a SxIP motif. iASPP silencing or mutation of the SxIP motif led to defective microtubule capture at the leading edge of migrating cells, and at the cortex of mitotic cells leading to abnormal positioning of the mitotic spindle. These effects were recapitulated by the knockdown of Myosin-Ic (Myo1c), identified as a novel partner of iASPP. Moreover, iASPP or Myo1c knockdown cells failed to round up during mitosis because of defective cortical rigidity. We propose that iASPP, together with EB1 and Myo1c, contributes to mitotic cell cortex rigidity, allowing astral microtubule capture and appropriate positioning of the mitotic spindle.

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RAB6 and microtubules restrict protein secretion to focal adhesions

Cited by 91 publications

References 41 publications

Loss of BICD2 in muscle drives motor neuron loss in a developmental form of spinal muscular atrophy

Loss of BICD2 in muscle drives motor neuron loss in a developmental form of spinal muscular atrophy

Direct trafficking pathways from the Golgi apparatus to the plasma membrane

iASPP contributes to cortex rigidity, astral microtubule capture and mitotic spindle positioning

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