A Primary Role for Golgi Positioning in Directed Secretion, Cell Polarity, and Wound Healing

Yadav, Smita; Puri, Sapna; Linstedt, Adam D.

doi:10.1091/mbc.e08-10-1077

Cited by 272 publications

(329 citation statements)

References 45 publications

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“…The interaction of the Golgi with the dynein1 complex is critical for both compaction of the Golgi and maintenance of Golgi stacks (27). Disruption of directional Golgi orientation by loss of golgins, golgin-160 and GMAP210, impairs directional cell migration and wound healing, demonstrating a direct relationship between polarization of Golgi stacks and directional migration (28). It is likely that the relationship between Golgi orientation (apical pole) and rotational motion involves similar mechanisms, highlighting the need to understand how cells establish and coordinate directionality during rotation.…”

Section: Discussionmentioning

confidence: 99%

Rotational motion during three-dimensional morphogenesis of mammary epithelial acini relates to laminin matrix assembly

Wang

Lacoche

Huang

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

123

110

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Our understanding of the mechanisms by which ducts and lobules develop is derived from model organisms and three-dimensional (3D) cell culture models wherein mammalian epithelial cells undergo morphogenesis to form multicellular spheres with a hollow central lumen. However, the mechanophysical properties associated with epithelial morphogenesis are poorly understood. We performed multidimensional live-cell imaging analysis to track the morphogenetic process starting from a single cell to the development of a multicellular, spherical structure composed of polarized epithelial cells surrounding a hollow lumen. We report that in addition to actively maintaining apicobasal polarity, the structures underwent rotational motions at rates of 15-20 μm/h and the structures rotated 360°every 4 h during the early phase of morphogenesis. Rotational motion was independent of the cell cycle, but was blocked by loss of the epithelial polarity proteins Scribble or Pard3, or by inhibition of dynein-based microtubule motors. Interestingly, none of the structures derived from human cancer underwent rotational motion. We found a direct relationship between rotational motion and assembly of endogenous basement membrane matrix around the 3D structures, and that structures that failed to rotate were defective in weaving exogenous laminin matrix. Dissolution of basement membrane around mature, nonrotating acini restored rotational movement and the ability to assemble exogenous laminin. Thus, coordinated rotational movement is a unique mechanophysical process observed during normal 3D morphogenesis that regulates laminin matrix assembly and is lost in cancer-derived epithelial cells. extracellular matrix | tubulogenesis | plasticity T issues are composed of a community of cells that act in a coordinated manner to achieve and maintain normal architecture and perform their function. The mechanisms by which cells coordinate their behavior during tissue morphogenesis is poorly understood in part due to technical bottlenecks associated with studying the process in vivo. Three-dimensional (3D) culture systems provide an environment in which normal tissue morphogenesis can be recapitulated and thus is a powerful tool for investigating the molecular signals that specify epithelial tissue architecture (1-3). Unlike monolayer cultures, epithelial cells grown in 3D recapitulate numerous features seen in vivo, including the formation of acini-like spheroids with a hollow lumen, apicobasal polarization of cells comprising these acini, and the deposition of basement membrane components collagen IV and laminin-332 (2).The initial stages of 3D morphogenesis are characterized by the ability of epithelial cells to detect surfaces with which they come in contact. Cells use integrins and dystroglycans to contact the extracellular matrix (ECM), and cadherins and desmosomes to contact their neighbors (3). These initial contacts trigger a series of cell remodeling events, which result in polarization of cells to create a basolateral surface and an apical surfa...

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Section: Discussionmentioning

confidence: 99%

Rotational motion during three-dimensional morphogenesis of mammary epithelial acini relates to laminin matrix assembly

Wang

Lacoche

Huang

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

123

110

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“…A large body of evidence suggests important roles for polarized localization of the Golgi (36). Cell migration requires polarized secretion at the leading edge for the regulated transport of vesicles, the delivery of adhesion molecules and cytoskeletal components, as well as the addition of new membranes.…”

Section: Discussionmentioning

confidence: 99%

Structure-Function Analysis of Core STRIPAK Proteins

Kean

Ceccarelli

Goudreault

et al. 2011

Journal of Biological Chemistry

137

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We show that striatins and CCM3 regulate the Golgi localization of MST4 in an opposite manner. Consistent with a previously described function for MST4 and CCM3 in Golgi positioning, depletion of CCM3 or striatins affects Golgi polarization, also in an opposite manner. We propose that STRIPAK regulates the balance between MST4 localization at the Golgi and in the cytosol to control Golgi positioning.

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“…Cell culture, transfections, immunofluorescence microscopy, image analysis, and immunoblot analyses were done as described by us previously (15,19,20,40,41). Tertiary structure of SPCA1 was derived using the algorithms of the MODBASE server (http://modbase.compbio.ucsf.edu/modbase-cgi/index.…”

Section: Methodsmentioning

confidence: 99%

“…port of the temperature-sensitive mutant of vesicular stomatitis virus G protein (VSVG) tagged with GFP (19,20). VSVG-GFP trafficking in cells expressing SPCA1-Q747A was indistinguishable from controls, in each case reaching the Golgi in 20 min and the cell surface in 60 min (Fig.…”

mentioning

confidence: 99%

Identification of a gain-of-function mutation in a Golgi P-type ATPase that enhances Mn ²⁺ efflux and protects against toxicity

Mukhopadhyay

Linstedt

2010

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

110

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P-type ATPases transport a wide array of ions, regulate diverse cellular processes, and are implicated in a number of human diseases. However, mechanisms that increase ion transport by these ubiquitous proteins are not known. SPCA1 is a P-type pump that transports Mn 2+ from the cytosol into the Golgi. We developed an intra-Golgi Mn 2+ sensor and used it to screen for mutations introduced in SPCA1, on the basis of its predicted structure, which could increase its Mn 2+ pumping activity. Remarkably, a point mutation (Q747A) predicted to increase the size of its ion permeation cavity enhanced the sensor response and a compensatory mutation restoring the cavity to its original size abolished this effect. In vivo and in vitro Mn 2+ transport assays confirmed the hyperactivity of SPCA1-Q747A. Furthermore, increasing Golgi Mn 2+ transport by expression of SPCA1-Q747A increased cell viability upon Mn 2+ exposure, supporting the therapeutic potential of increased Mn 2+ uptake by the Golgi in the management of Mn 2+ -induced neurotoxicity.manganese | membrane trafficking | secretion | GPP130

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A Primary Role for Golgi Positioning in Directed Secretion, Cell Polarity, and Wound Healing

Cited by 272 publications

References 45 publications

Rotational motion during three-dimensional morphogenesis of mammary epithelial acini relates to laminin matrix assembly

Rotational motion during three-dimensional morphogenesis of mammary epithelial acini relates to laminin matrix assembly

Structure-Function Analysis of Core STRIPAK Proteins

Identification of a gain-of-function mutation in a Golgi P-type ATPase that enhances Mn ²⁺ efflux and protects against toxicity

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A Primary Role for Golgi Positioning in Directed Secretion, Cell Polarity, and Wound Healing

Cited by 272 publications

References 45 publications

Rotational motion during three-dimensional morphogenesis of mammary epithelial acini relates to laminin matrix assembly

Rotational motion during three-dimensional morphogenesis of mammary epithelial acini relates to laminin matrix assembly

Structure-Function Analysis of Core STRIPAK Proteins

Identification of a gain-of-function mutation in a Golgi P-type ATPase that enhances Mn 2+ efflux and protects against toxicity

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Identification of a gain-of-function mutation in a Golgi P-type ATPase that enhances Mn ²⁺ efflux and protects against toxicity