scholarly journals Specialized protrusions coordinate migratory border cell cluster cohesion via Scribble, Cdep, and Rac

2022 ◽  
Author(s):  
Joseph P Campanale ◽  
James A Mondo ◽  
Denise J Montell
Keyword(s):  
Protein Localization ◽  
Effector Proteins ◽  
Cell Cluster ◽  
Follicular Epithelium ◽  
Nucleotide Exchange ◽  
Major Function ◽  
Border Cell ◽  
Egg Chambers ◽  
And Migration ◽  
And Function

Apicobasal polarity is a defining characteristic of epithelial cells and its disruption is a cancer hallmark. Distinct apical and basolateral protein modules antagonize each other to establish separate membrane domains. These modules interact with dozens of potential effector proteins. Here we describe polarity protein localization and function within a migrating epithelial cell cluster and identify a functionally significant effector protein. In Drosophila egg chambers, border cells delaminate from the follicular epithelium and migrate collectively. We report that the basolateral protein Scribble is required for border cell cluster cohesion and migration. The basolateral module localizes the Rac guanine nucleotide exchange factor Cdep to membranes, and Cdep knockdown phenocopies Scribble cluster cohesion defects. Remarkably, membrane targeting of Cdep is sufficient to partially suppress multiple Scribble phenotypes. We describe specialized basolateral protrusions that promote cluster cohesion. Scribble restricts these protrusions from encroaching onto the apical domain. Thus, a major function of the basolateral module is to localize Cdep, promoting specialized protrusions, cluster cohesion, and collective migration.

scholarly journals Imaging the migrating border cell cluster in livingDrosophila egg chambers

2007 ◽  
Vol 236 (10) ◽  
pp. 2818-2824 ◽  
Author(s):  
Hille Tekotte ◽  
David Tollervey ◽  
Ilan Davis
Keyword(s):  
Cell Cluster ◽  
Border Cell ◽  
Egg Chambers

scholarly journals Septate junction proteins are required for egg elongation and border cell migration during oogenesis in Drosophila

2021 ◽  
Author(s):  
Haifa Alhadyian ◽  
Dania Shoaib ◽  
Robert E Ward
Keyword(s):  
Drosophila Melanogaster ◽  
Cell Migration ◽  
Developmental Stages ◽  
Septate Junction ◽  
Follicle Cells ◽  
Follicular Epithelium ◽  
Border Cell ◽  
Egg Chambers ◽  
Border Cell Migration ◽  
Protein Components

Abstract Protein components of the invertebrate occluding junction—known as the septate junction (SJ) - are required for morphogenetic developmental events during embryogenesis in Drosophila melanogaster. In order to determine whether SJ proteins are similarly required for morphogenesis during other developmental stages, we investigated the localization and requirement of four representative SJ proteins during oogenesis: Contactin, Macroglobulin complement-related, Neurexin IV, and Coracle. A number of morphogenetic processes occur during oogenesis, including egg elongation, formation of dorsal appendages, and border cell migration. We found that all four SJ proteins are expressed in egg chambers throughout oogenesis, with the highest and most sustained levels in the follicular epithelium (FE). In the FE, SJ proteins localize along the lateral membrane during early and mid-oogenesis, but become enriched in an apical-lateral domain (the presumptive SJ) by stage 10B. SJ protein relocalization requires the expression of other SJ proteins, as well as Rab5 and Rab11 in a manner similar to SJ biogenesis in the embryo. Knocking down the expression of these SJ proteins in follicle cells throughout oogenesis results in egg elongation defects and abnormal dorsal appendages. Similarly, reducing the expression of SJ genes in the border cell cluster results in border cell migration defects. Together, these results demonstrate an essential requirement for SJ genes in morphogenesis during oogenesis, and suggests that SJ proteins may have conserved functions in epithelial morphogenesis across developmental stages. Article Summary: Septate junction (SJ) proteins are essential for forming an occluding junction in epithelial tissues in Drosophila melanogaster, and also for morphogenetic events that occur prior to the formation of the junction during embryogenesis. Here we show that SJ proteins are expressed in the follicular epithelium of egg chambers during oogenesis and are required for morphogenetic events including egg elongation, dorsal appendages formation, and border cell migration. Additionally, the formation of SJs during oogenesis is similar to that in embryonic epithelia.

POPDC proteins and cardiac function

2019 ◽  
Vol 47 (5) ◽  
pp. 1393-1404 ◽  
Author(s):  
Thomas Brand
Keyword(s):  
Potential Role ◽  
Striated Muscle ◽  
Short Review ◽  
Effector Proteins ◽  
Muscle Disease ◽  
Disease Genes ◽  
Protein Protein Interaction ◽  
Interaction Partners ◽  
And Function

Abstract The Popeye domain-containing gene family encodes a novel class of cAMP effector proteins in striated muscle tissue. In this short review, we first introduce the protein family and discuss their structure and function with an emphasis on their role in cyclic AMP signalling. Another focus of this review is the recently discovered role of POPDC genes as striated muscle disease genes, which have been associated with cardiac arrhythmia and muscular dystrophy. The pathological phenotypes observed in patients will be compared with phenotypes present in null and knockin mutations in zebrafish and mouse. A number of protein–protein interaction partners have been discovered and the potential role of POPDC proteins to control the subcellular localization and function of these interacting proteins will be discussed. Finally, we outline several areas, where research is urgently needed.

scholarly journals Climate Mobility and Development Cooperation

2021 ◽  
Author(s):  
Robert Stojanov ◽  
Sarah Rosengaertner ◽  
Alex de Sherbinin ◽  
Raphael Nawrotzki
Keyword(s):  
Climate Adaptation ◽  
Human Mobility ◽  
Climate Impacts ◽  
Development Cooperation ◽  
Climate Variability And Change ◽  
Policy Frameworks ◽  
And Migration ◽  
And Function ◽  
Role And Function

AbstractDevelopment cooperation actors have been addressing climate change as a cross-cutting issue and investing in climate adaptation projects since the early 2000s. More recently, as concern has risen about the potential impacts of climate variability and change on human mobility, development cooperation actors have begun to design projects that intentionally address the drivers of migration, including climate impacts on livelihoods. However, to date, we know little about the development cooperation’s role and function in responding to climate related mobility and migration. As such, the main aim of this paper is to outline the policy frameworks and approaches shaping development cooperation actors’ engagement and to identify areas for further exploration and investment. First, we frame the concept of climate mobility and migration and discuss some applicable policy frameworks that govern the issue from various perspectives; secondly, we review the toolbox of approaches that development cooperation actors bring to climate mobility; and third, we discuss the implications of the current Covid-19 pandemic and identify avenues for the way forward. We conclude that ensuring safe and orderly mobility and the decent reception and long-term inclusion of migrants and displaced persons under conditions of more severe climate hazards, and in the context of rising nationalism and xenophobia, poses significant challenges. Integrated approaches across multiple policy sectors and levels of governance are needed. In addition to resources, development cooperation actors can bring data to help empower the most affected communities and regions and leverage their convening power to foster more coordinated approaches within and across countries.

scholarly journals EMT Participates in the Regulation of Exosomes Secretion and Function in Esophageal Cancer Cells

2021 ◽  
Vol 20 ◽  
pp. 153303382110330
Author(s):  
Chuangui Chen ◽  
Zhao Ma ◽  
Hongjing Jiang
Keyword(s):  
Esophageal Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Promoting Effect ◽  
Migration Ability ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
And Migration ◽  
And Function ◽  
Esophageal Cancer Cells

Epithelial-mesenchymal transition (EMT) is a key step in tumor invasion and distant metastasis. Abundant evidence has documented that exosomes can mediate EMT of tumor cells and endow them with the ability of invasion and migration. However, there are few studies focusing on whether EMT can reverse the secretion of exosomes. In this study, 2 esophageal cancer cells (FLO-1 and SK-GT-4) were selected to compare the migration ability and EMT activation, and to further analyze the secretion ability of exosomes of the 2 cell lines. According to the results, inhibited activation of EMT in FLO-1 cells with relatively high migration ability could effectively reduce the secretion of exosomes. Besides, in SK-GT-4 cells, EMT activation induced by TGF-β could promote the secretion of exosomes. FLO-1 cell derived exosomes exhibited a paracrine effect of promoting the migration of SK-GT-4 cells, and the use of EMT inhibitors could weaken this ability. Furthermore, inhibition of EMT could change the relative content of some miRNAs in exosomes, with a particularly significant downregulation in the expression of miR-196-5p, miR-21-5p and miR-194-5p. Significantly, artificial transfection of the 3 miRNAs into exosomes by electroporation resulted in the recovery of migration-promoting effect of exosomes. Subsequent experiments further revealed that the effect of EMT on these miRNAs could be explained by the intracellular transcription level or the specific sorting mechanism of exosomes. To sum up, our study undoubtedly reveals that EMT has a regulatory effect on exosomes in the quantity and contents in esophageal cancer cells. Significantly, findings in our study provide experimental evidence for the interaction of EMT with the secretion and sorting pathway of exosomes, and also give a new direction for the further study of tumor metastasis.

scholarly journals ADP-Ribosylation Factor (ARF) Interaction Is Not Sufficient for Yeast GGA Protein Function or Localization

2002 ◽  
Vol 13 (9) ◽  
pp. 3078-3095 ◽  
Author(s):  
Annette L. Boman ◽  
Paul D. Salo ◽  
Melissa J. Hauglund ◽  
Nicole L. Strand ◽  
Shelly J. Rensink ◽  
...  
Keyword(s):  
Membrane Trafficking ◽  
Mammalian Cells ◽  
Fluorescent Protein ◽  
Protein Localization ◽  
Carboxypeptidase Y ◽  
Minor Role ◽  
Temperature Sensitive ◽  
Adp Ribosylation ◽  
And Function ◽  
Adp Ribosylation Factor

Golgi-localized γ-ear homology domain, ADP-ribosylation factor (ARF)-binding proteins (GGAs) facilitate distinct steps of post-Golgi traffic. Human and yeast GGA proteins are only ∼25% identical, but all GGA proteins have four similar domains based on function and sequence homology. GGA proteins are most conserved in the region that interacts with ARF proteins. To analyze the role of ARF in GGA protein localization and function, we performed mutational analyses of both human and yeast GGAs. To our surprise, yeast and human GGAs differ in their requirement for ARF interaction. We describe a point mutation in both yeast and mammalian GGA proteins that eliminates binding to ARFs. In mammalian cells, this mutation disrupts the localization of human GGA proteins. Yeast Gga function was studied using an assay for carboxypeptidase Y missorting and synthetic temperature-sensitive lethality between GGAs andVPS27. Based on these assays, we conclude that non-Arf-binding yeast Gga mutants can function normally in membrane trafficking. Using green fluorescent protein-tagged Gga1p, we show that Arf interaction is not required for Gga localization to the Golgi. Truncation analysis of Gga1p and Gga2p suggests that the N-terminal VHS domain and C-terminal hinge and ear domains play significant roles in yeast Gga protein localization and function. Together, our data suggest that yeast Gga proteins function to assemble a protein complex at the late Golgi to initiate proper sorting and transport of specific cargo. Whereas mammalian GGAs must interact with ARF to localize to and function at the Golgi, interaction between yeast Ggas and Arf plays a minor role in Gga localization and function.

scholarly journals The Scaffold Protein Cybr Is Required for Cytokine-Modulated Trafficking of Leukocytes In Vivo

2006 ◽  
Vol 26 (14) ◽  
pp. 5249-5258 ◽  
Author(s):  
Vincenzo Coppola ◽  
Colleen A. Barrick ◽  
Sara Bobisse ◽  
Maria Cecilia Rodriguez-Galan ◽  
Michela Pivetta ◽  
...  
Keyword(s):  
Immune System ◽  
Cytotoxic T Lymphocyte ◽  
Leukemia Virus ◽  
Physiological Role ◽  
Scaffold Protein ◽  
Nucleotide Exchange ◽  
Lymphocyte Migration ◽  
And Migration

ABSTRACT Trafficking and cell adhesion are key properties of cells of the immune system. However, the molecular pathways that control these cellular behaviors are still poorly understood. Cybr is a scaffold protein highly expressed in the hematopoietic/immune system whose physiological role is still unknown. In vitro studies have shown it regulates LFA-1, a crucial molecule in lymphocyte attachment and migration. Cybr also binds cytohesin-1, a guanine nucleotide exchange factor for the ARF GTPases, which affects actin cytoskeleton remodeling during cell migration. Here we show that expression of Cybr in vivo is differentially modulated by type 1 cytokines during lymphocyte maturation. In mice, Cybr deficiency negatively affects leukocytes circulating in blood and lymphocytes present in the lymph nodes. Moreover, in a Th1-polarized mouse model, lymphocyte trafficking is impaired by loss of Cybr, and Cybr-deficient mice with aseptic peritonitis have fewer cells than controls present in the peritoneal cavity, as well as fewer leukocytes leaving the bloodstream. Mutant mice injected with Moloney murine sarcoma/leukemia virus develop significantly larger tumors than wild-type mice and have reduced lymph node enlargement, suggesting reduced cytotoxic T-lymphocyte migration. Taken together, these data support a role for Cybr in leukocyte trafficking, especially in response to proinflammatory cytokines in stress conditions.

scholarly journals Disparate Subcellular Localization Patterns of Pseudomonas aeruginosa Type IV Pilus ATPases Involved in Twitching Motility

2005 ◽  
Vol 187 (3) ◽  
pp. 829-839 ◽  
Author(s):  
Poney Chiang ◽  
Marc Habash ◽  
Lori L. Burrows
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Fluorescent Protein ◽  
Protein Localization ◽  
Yellow Fluorescent Protein ◽  
Distribution Patterns ◽  
Opportunistic Pathogen ◽  
Twitching Motility ◽  
Polar Localization ◽  
Type Iv ◽  
And Function

ABSTRACT The opportunistic pathogen Pseudomonas aeruginosa expresses polar type IV pili (TFP), which are responsible for adhesion to various materials and twitching motility on surfaces. Twitching occurs by alternate extension and retraction of TFP, which arise from assembly and disassembly of pilin subunits at the base of the pilus. The ATPase PilB promotes pilin assembly, while the ATPase PilT or PilU or both promote pilin dissociation. Fluorescent fusions to two of the three ATPases (PilT and PilU) were functional, as shown by complementation of the corresponding mutants. PilB and PilT fusions localized to both poles, while PilU fusions localized only to the piliated pole. To identify the portion of the ATPases required for localization, sequential C-terminal deletions of PilT and PilU were generated. The conserved His and Walker B boxes were dispensable for polar localization but were required for twitching motility, showing that localization and function could be uncoupled. Truncated fusions that retained polar localization maintained their distinctive distribution patterns. To dissect the cellular factors involved in establishing polarity, fusion protein localization was monitored with a panel of TFP mutants. The localization of yellow fluorescent protein (YFP)-PilT and YFP-PilU was independent of the subunit PilA, other TFP ATPases, and TFP-associated proteins previously shown to be associated with the membrane or exhibiting polar localization. In contrast, YFP-PilB exhibited diffuse cytoplasmic localization in a pilC mutant, suggesting that PilC is required for polar localization of PilB. Finally, localization studies performed with fluorescent ATPase chimeras of PilT and PilU demonstrated that information responsible for the characteristic localization patterns of the ATPases likely resides in their N termini.

scholarly journals Stage-specific Localization and Expression of c-kit in the Adult Human Testis

2009 ◽  
Vol 57 (9) ◽  
pp. 861-869 ◽  
Author(s):  
Sreepoorna K. Unni ◽  
Deepak N. Modi ◽  
Shilpa G. Pathak ◽  
Jayesh V. Dhabalia ◽  
Deepa Bhartiya
Keyword(s):  
Current Knowledge ◽  
Protein Localization ◽  
Immunohistochemical Analysis ◽  
Human Testis ◽  
Specific Expression ◽  
Adult Human ◽  
Kit Receptor ◽  
Specific Localization ◽  
Human Spermatogenesis ◽  
And Function

The c-kit receptor (KIT) and its ligand, stem cell factor (SCF), represent one of the key regulators of testicular formation, development, and function and have been extensively studied in various animal models. The present study was undertaken to characterize the pattern of localization and expression of c-kit in normal adult human testis. Immunohistochemical analysis showed that KIT is expressed in the cytoplasm of spermatogonia, acrosomal granules of spermatids, and Leydig cells. Interestingly, a rather heterogenous pattern of expression of the protein along the basement membrane was observed. Intense protein localization in spermatogonia was detected in stages I–III, whereas low expression was observed in stages IV–VI of the seminiferous epithelium, indicating that the expression of the molecule was stage specific. In situ hybridization studies revealed that the transcripts of the gene were also localized in a similar non-uniform pattern. To the best of our knowledge, such a stage-specific expression of KIT has not been reported previously in the human testis. The results of the present study may expand current knowledge about the c-kit/SCF system in human spermatogenesis.

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