maritabo

• Aas, Sigve Nyvik; Distefano, Marita Borg; Pettersen, Ingvild; Gravrok, Berit; Nordvoll, Laila Yvonne & Bjåstad, Jon Fauskanger [Vis alle 7 forfattere av denne artikkelen] (2023). Patient and public involvement in health research in Norway: a survey among researchers and patient organisations. Research Involvement and Engagement. 9(1). doi: 10.1186/s40900-023-00458-x. Fulltekst i vitenarkiv Vis sammendrag

  Background - Patient and public involvement (PPI) in health research may improve both the relevance and quality of the research. There is however a lack of research investigating the experiences, attitudes and barriers towards PPI in clinical research in Norway. The Norwegian Clinical Research Infrastructure Network therefore conducted a survey among researchers and PPI contributors aiming to investigate experiences with PPI and identify current challenges for successful involvement. Methods - Two survey questionnaires were developed and distributed in October and November 2021. The survey targeting 1185 researchers was distributed from the research administrative system in the Regional Health Trusts. The survey targeting PPI contributors was distributed through Norwegian patient organisations, regional and national competence centers. Results - The response rate was 30% among researchers and was unobtainable from PPI contributors due to the survey distribution strategy. PPI was most frequently used in the planning and conduct of the studies, and less utilized in dissemination and implementation of results. Both researchers and user representatives were generally positive to PPI, and agreed that PPI might be more useful in clinical research than in underpinning research. Researchers and PPI contributors who reported that roles and expectations were clarified in advance, were more likely to experience a common understanding of roles and responsibilities in the research project. Both groups pointed to the importance of earmarked funding for PPI activities. There was a demand for a closer collaboration between researchers and patient organisations to develop accessible tools and effective models for PPI in health research. Conclusions - Surveys among clinical researchers and PPI contributors indicate overall positive attitudes towards PPI in clinical research. However, more resources, such as budget, time, and accessible tools, are needed. Clarifying roles and expectations, and creating new PPI models under resource constraints can enhance its effectiveness. PPI is underutilized in disseminating and implementing research results, presenting an opportunity for improving healthcare outcomes.

• Vestre, Katharina; Persiconi, Irene; Distefano, Marita Borg; Mensali, Nadia; Guadagno, Noemi Antonella & Bretou, Marine [Vis alle 12 forfattere av denne artikkelen] (2021). Rab7b regulates dendritic cell migration by linking lysosomes to the actomyosin cytoskeleton. Journal of Cell Science. ISSN 0021-9533. 134(18). doi: 10.1242/jcs.259221. Fulltekst i vitenarkiv Vis sammendrag

  Lysosomal signaling facilitates the migration of immune cells by releasing calcium to activate the actin-based motor myosin II at the cell rear. However, how the actomyosin cytoskeleton physically associates to lysosomes is unknown. We have previously identified myosin II as a direct interactor of Rab7b, a small GTPase that mediates the transport from late endosomes/lysosomes to the TGN. Here, we show that Rab7b regulates the migration of dendritic cells (DCs) in 1- and 3-dimensional environments. DCs are immune sentinels that transport antigens from peripheral tissues to lymph nodes to activate T lymphocytes and initiate adaptive immune responses. We found that lack of Rab7b reduces myosin II light chain phosphorylation and the activation of the transcription factor EB (TFEB), which controls lysosomal signaling and is required for fast DC migration. Furthermore, we demonstrate that Rab7b interacts with the lysosomal calcium channel TRPML1, enabling the local activation of myosin II at the cell rear. Altogether, our findings identify Rab7b as the missing physical link between lysosomes and the actomyosin cytoskeleton, allowing control of immune cell migration through lysosomal signaling.

• Vestre, Katharina; Kjos, Ingrid; Guadagno, Noemi Antonella; Distefano, Marita Borg; Kohler, Felix & Fenaroli, Federico [Vis alle 8 forfattere av denne artikkelen] (2019). Rab6 regulates cell migration and invasion by recruiting Cdc42 and modulating its activity. Cellular and Molecular Life Sciences (CMLS). ISSN 1420-682X. 76(13), s. 2593–2614. doi: 10.1007/s00018-019-03057-w. Fulltekst i vitenarkiv Vis sammendrag

  Rab proteins are master regulators of intracellular membrane trafficking, but they also contribute to cell division, signaling, polarization, and migration. The majority of the works describing the mechanisms used by Rab proteins to regulate cell motility involve intracellular transport of key molecules important for migration. Interestingly, a few studies indicate that Rabs can modulate the activity of Rho GTPases, important regulators for the cytoskeleton rearrangements, but the mechanisms behind this crosstalk are still poorly understood. In this work, we identify Rab6 as a negative regulator of cell migration in vitro and in vivo. We show that the loss of Rab6 promotes formation of actin protrusions and influences actomyosin dynamics by upregulating Cdc42 activity and downregulating myosin II phosphorylation. We further provide the molecular mechanism behind this regulation demonstrating that Rab6 interacts with both Cdc42 and Trio, a GEF for Cdc42. In sum, our results uncover a mechanism used by Rab proteins to ensure spatial regulation of Rho GTPase activity for coordination of cytoskeleton rearrangements required in migrating cells.

• Kjos, Ingrid; Vestre, Katharina; Guadagno, Noemi Antonella; Distefano, Marita Borg & Progida, Cinzia (2018). Rab and Arf proteins at the crossroad between membrane transport and cytoskeleton dynamics. BBA - Molecular Cell Research. ISSN 0167-4889. 1865(10), s. 1397–1409. doi: 10.1016/j.bbamcr.2018.07.009. Fulltekst i vitenarkiv Vis sammendrag

  The intracellular movement and positioning of organelles and vesicles is mediated by the cytoskeleton and molecular motors. Small GTPases like Rab and Arf proteins are main regulators of intracellular transport by connecting membranes to cytoskeleton motors or adaptors. However, it is becoming clear that interactions between these small GTPases and the cytoskeleton are important not only for the regulation of membrane transport. In this review, we will cover our current understanding of the mechanisms underlying the connection between Rab and Arf GTPases and the cytoskeleton, with special emphasis on the double role of these interactions, not only in membrane trafficking but also in membrane and cytoskeleton remodeling. Furthermore, we will highlight the most recent findings about the fine control mechanisms of crosstalk between different members of Rab, Arf, and Rho families of small GTPases in the regulation of cytoskeleton organization.

• Distefano, Marita Borg; Haugen, Linda Hofstad; Wang, Yan; Perdreau-Dahl, Harmonie; Kjos, Ingrid & Jia, Da [Vis alle 10 forfattere av denne artikkelen] (2018). TBC1D5 controls the GTPase cycle of Rab7b. Journal of Cell Science. ISSN 0021-9533. 131(17), s. 1–13. doi: 10.1242/jcs.216630. Fulltekst i vitenarkiv Vis sammendrag

  Rab GTPases are key regulators of intracellular trafficking, and cycle between a GTP-bound active state and a GDP-bound inactive state. This cycle is regulated by guanine-nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). Several efforts have been made in connecting the correct GEFs and GAPs to their specific Rab. Here, we aimed to identify GAPs for Rab7b, the small GTPase involved in transport from late endosomes to the trans-Golgi. An siRNA screen targeting proteins containing TBC domains critical for Rab GAPs was performed and coupled to a phenotypic read-out that visualized the distribution of Rab7b. Silencing of TBC1D5 provided the strongest phenotype and this protein was subsequently validated in various in vitro and cell-based assays. TBC1D5 localizes to Rab7b-positive vesicles, interacts with Rab7b and has GAP activity towards Rab7b in vitro, which is further increased by retromer proteins. Similarly to the constitutively active mutant of Rab7b, inactivation of TBC1D5 also reduces the number of CI-MPR- and sortilin-positive vesicles. Together, the results show that TBC1D5 is a GAP for Rab7b in the control of endosomal transport to the trans-Golgi.

• Kjos, Ingrid; Distefano, Marita Borg; Sætre, Frank Ove; Repnik, Urska; Holland, Petter & Jones, Arwyn T [Vis alle 10 forfattere av denne artikkelen] (2017). Rab7b modulates autophagic flux by interacting with Atg4B. EMBO Reports. ISSN 1469-221X. 18(10), s. 1727–1739. doi: 10.15252/embr.201744069. Fulltekst i vitenarkiv Vis sammendrag

  Autophagy (macroautophagy) is a highly conserved eukaryotic degradation pathway in which cytosolic components and organelles are sequestered by specialized autophagic membranes and degraded through the lysosomal system. The autophagic pathway maintains basal cellular homeostasis and helps cells adapt during stress; thus, defects in autophagy can cause detrimental effects. It is therefore crucial that autophagy is properly regulated. In this study, we show that the cysteine protease Atg4B, a key enzyme in autophagy that cleaves LC3, is an interactor of the small GTPase Rab7b. Indeed, Atg4B interacts and co‐localizes with Rab7b on vesicles. Depletion of Rab7b increases autophagic flux as indicated by the increased size of autophagic structures as well as the magnitude of macroautophagic sequestration and degradation. Importantly, we demonstrate that Rab7b regulates LC3 processing by modulating Atg4B activity. Taken together, our findings reveal Rab7b as a novel negative regulator of autophagy through its interaction with Atg4B.

• Repnik, Urska; Distefano, Marita Borg; Speth, Martin; NG, Matthew Yoke Wui; Progida, Cinzia & Hoflack, Bernard [Vis alle 8 forfattere av denne artikkelen] (2017). L-leucyl-L-leucine methyl ester does not release cysteine cathepsins to the cytosol but inactivates them in transiently permeabilized lysosomes. Journal of Cell Science. ISSN 0021-9533. 130(18), s. 3124–3140. doi: 10.1242/jcs.204529. Fulltekst i vitenarkiv
• Kucera, Ana; Distefano, Marita Borg; Berg-Larsen, Axel; Skjeldal, Frode Miltzow; Repnik, Urska & Bakke, Oddmund [Vis alle 7 forfattere av denne artikkelen] (2016). Spatiotemporal Resolution of Rab9 and CI-MPR Dynamics in the Endocytic Pathway. Traffic: The moving front of cell biology. ISSN 1398-9219. 17(3), s. 211–229. doi: 10.1111/tra.12357. Fulltekst i vitenarkiv
• Distefano, Marita Borg; Kjos, Ingrid; Bakke, Oddmund & Progida, Cinzia (2015). Rab7b at the intersection of intracellular trafficking and cell migration. Communicative & Integrative Biology. 8(6). doi: 10.1080/19420889.2015.1023492. Fulltekst i vitenarkiv
• Borg, Marita Jeanett Halsen; Bakke, Oddmund & Progida, Cinzia (2014). A novel interaction between Rab7b and actomyosin reveals a dual role in intracellular transport and cell migration. Journal of Cell Science. ISSN 0021-9533. 127(22), s. 4927–4939. doi: 10.1242/jcs.155861. Fulltekst i vitenarkiv

Se alle arbeider i NVA

• Bjåstad, Jon Fauskanger; Aas, Sigve Nyvik; Distefano, Marita Borg; Berglen, Gunnhild; Haugen, Nikolai Raaby & Gjestsen, Martha Therese [Vis alle 11 forfattere av denne artikkelen] (2024). Brukermedvirkning i forskning – for lite, for sent. doi: 10.4045/tidsskr.23.0684. Fulltekst i vitenarkiv
• Distefano, Marita Borg (2018). First person - Marita Borg Distefano. [Journal]. Journal of Cell Science. doi: 10.1242/jcs.223875. Fulltekst i vitenarkiv

Se alle arbeider i NVA