Sec15, a Component of the Exocyst, Promotes Notch Signaling during the Asymmetric Division of Drosophila Sensory Organ Precursors

Jafar‐Nejad, Hamed; Andrews, Hillary K.; Acar, Melih; Bayat, Vafa; Wirtz-Peitz, Frederik; Mehta, Sunil; Knoblich, Juergen A.; Bellen, Hugo J.

doi:10.1016/j.devcel.2005.06.010

Cited by 186 publications

(206 citation statements)

References 79 publications

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“…Low levels of Rab11DN gave mild developmental defects (supplemental Figure 2B at http:/ /www.genetics.org/supplemental/) compared to control flies (supplemental Figure 2A at http://www. genetics.org/supplemental/) and high levels caused massively reduced eyes or even lethality (data not shown), confirming a previously reported cell lethality of dominant-negative Rab11 (Emery et al 2005;Jafar-Nejad et al 2005).…”

Section: Resultssupporting

confidence: 88%

Thirty-One Flavors of Drosophila Rab Proteins

et al. 2007

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Rab proteins are small GTPases that play important roles in transport of vesicle cargo and recruitment, association of motor and other proteins with vesicles, and docking and fusion of vesicles at defined locations. In vertebrates, .75 Rab genes have been identified, some of which have been intensively studied for their roles in endosome and synaptic vesicle trafficking. Recent studies of the functions of certain Rab proteins have revealed specific roles in mediating developmental signal transduction. We have begun a systematic genetic study of the 33 Rab genes in Drosophila. Most of the fly proteins are clearly related to specific vertebrate proteins. We report here the creation of a set of transgenic fly lines that allow spatially and temporally regulated expression of Drosophila Rab proteins. We generated fluorescent proteintagged wild-type, dominant-negative, and constitutively active forms of 31 Drosophila Rab proteins. We describe Drosophila Rab expression patterns during embryogenesis, the subcellular localization of some Rab proteins, and comparisons of the localization of wild-type, dominant-negative, and constitutively active forms of selected Rab proteins. The high evolutionary conservation and low redundancy of Drosophila Rab proteins make these transgenic lines a useful tool kit for investigating Rab functions in vivo.

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Section: Resultssupporting

confidence: 88%

Thirty-One Flavors of Drosophila Rab Proteins

et al. 2007

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“…It has been suggested that trafficking through Rab11-positive recycling endosomes ensures proper Delta activity (19). Sec15, an effector of Rab11 (20), has also been shown to be required for Delta recycling and signaling activity in signal-sending cells; however, direct evidence of ligand recycling has not been provided. Our experiments demonstrate that wt Dll1 is effectively endocytosed and recycled back to the cell surface, whereas Dll1K17R is endocytosed but not recycled.…”

Section: Several Authors Have Reported That Ubiquitination and Endocymentioning

confidence: 99%

The intracellular region of Notch ligands Dll1 and Dll3 regulates their trafficking and signaling activity

Heuss

Ndiaye‐Lobry

Six

et al. 2008

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

116

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Genetic studies have shown that ubiquitination and endocytosis of the Drosophila ligand Delta in signal-sending cells are required for activation of Notch signaling, but how these events promote Notch activation remains poorly understood. Here, we show that an ubiquitination-defective mutant of the murine Delta-homologue Dll1 is endocytosed but, in contrast to the wild-type Dll1, is unable to subsequently recycle back to the cell surface or to bind Notch1 efficiently. These results demonstrate that ubiquitination, although not required for endocytosis, is essential for Dll1 recycling and that recycling is required to acquire affinity for the receptor. On the other hand, a chimeric molecule encompassing the extracellular domain of Dll1 and the transmembrane/intracellular domain of Dll3, which contains no lysine, is endocytosed, recycled, and interacts with Notch1 but is unable to induce transendocytosis of the extracellular region of Notch1 or to signal. These observations suggest that the chimera uses an ubiquitination-independent signal to recycle, allowing it to acquire affinity for Notch1. Our results support the idea that ligand recycling determines its competence to bind efficiently to the receptor but that this is insufficient to allow it to perform transendocytosis, an event required for activation of Notch signaling. Finally, the present study indicates that Dll1 partially localizes to lipid microdomains, whereas both ubiquitination-defective Dll1 and the Dll1-3 chimera are excluded from these compartments, suggesting that these microdomains provide the environment necessary for Dll1 to activate Notch signaling.ubiquitination ͉ recycling ͉ transendocytosis ͉ membrane microdomains

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“…Clearly, there are numerous cellular components in addition to focal adhesions, such as cytoskeletal elements, protein trafficking components and ion channels that are involved in mechanical signaling and thus may also contribute to the regulation of durotaxis [13][14][15] . Each of these components could be readily evaluated in our system using similar RNAi approaches.…”

Section: Discussionmentioning

confidence: 99%

A Simplified System for Evaluating Cell Mechanosensing and Durotaxis <em>In Vitro</em>

Goreczny

Wormer

Turner

2015

JoVE

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The composition and mechanical properties of the extracellular matrix are highly variable between tissue types. This connective tissue stroma diversity greatly impacts cell behavior to regulate normal and pathologic processes including cell proliferation, differentiation, adhesion signaling and directional migration. In this regard, the innate ability of certain cell types to migrate towards a stiffer, or less compliant matrix substrate is referred to as durotaxis. This phenomenon plays an important role during embryonic development, wound repair and cancer cell invasion. Here, we describe a straightforward assay to study durotaxis, in vitro, using polydimethylsiloxane (PDMS) substrates. Preparation of the described durotaxis chambers creates a rigidity interface between the relatively soft PDMS gel and a rigid glass coverslip. In the example provided, we have used these durotaxis chambers to demonstrate a role for the cdc42/Rac1 GTPase activating protein, cdGAP, in mechanosensing and durotaxis regulation in human U2OS osteosarcoma cells. This assay is readily adaptable to other cell types and/or knockdown of other proteins of interests to explore their respective roles in mechanosignaling and durotaxis. Video LinkThe video component of this article can be found at

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Sec15, a Component of the Exocyst, Promotes Notch Signaling during the Asymmetric Division of Drosophila Sensory Organ Precursors

Cited by 186 publications

References 79 publications

Thirty-One Flavors of Drosophila Rab Proteins

Thirty-One Flavors of Drosophila Rab Proteins

The intracellular region of Notch ligands Dll1 and Dll3 regulates their trafficking and signaling activity

A Simplified System for Evaluating Cell Mechanosensing and Durotaxis <em>In Vitro</em>

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