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      Coordination between Rac1 and Rab Proteins: Functional Implications in Health and Disease

      review-article
      Author(s): 1 , * , 2 , *
      Publication date (Electronic):
      Journal: Cells
      Publisher: MDPI
      Keywords: Rac1, Rab proteins, actin cytoskeleton, GTPase, Rho proteins

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          Abstract

          The small GTPases of the Rho family regulate many aspects of actin dynamics, but are functionally connected to many other cellular processes. Rac1, a member of this family, besides its known function in the regulation of actin cytoskeleton, plays a key role in the production of reactive oxygen species, in gene transcription, in DNA repair, and also has been proven to have specific roles in neurons. This review focuses on the cooperation between Rac1 and Rab proteins, analyzing how the coordination between these GTPases impact on cells and how alterations of their functions lead to disease.

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          A molecular network for de novo generation of the apical surface and lumen.

          David M Bryant, Anirban Datta, Alejo E Rodríguez-Fraticelli … (2010)
          To form epithelial organs cells must polarize and generate de novo an apical domain and lumen. Epithelial polarization is regulated by polarity complexes that are hypothesized to direct downstream events, such as polarized membrane traffic, although this interconnection is not well understood. We have found that Rab11a regulates apical traffic and lumen formation through the Rab guanine nucleotide exchange factor (GEF), Rabin8, and its target, Rab8a. Rab8a and Rab11a function through the exocyst to target Par3 to the apical surface, and control apical Cdc42 activation through the Cdc42 GEF, Tuba. These components assemble at a transient apical membrane initiation site to form the lumen. This Rab11a-directed network directs Cdc42-dependent apical exocytosis during lumen formation, revealing an interaction between the machineries of vesicular transport and polarization.
          Article 0 comments Cited 214 times – based on 0 reviews     Review now
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            Innate and Adaptive Immune Memory: an Evolutionary Continuum in the Host’s Response to Pathogens

            Mihai Netea, Andreas Schlitzer, Katarzyna Placek … (2019)
            Immunological memory is an important evolutionary trait that improves host survival upon reinfection. Memory is a characteristic recognized within both the innate and adaptive arms of the immune system. Although the mechanisms and properties through which innate and adaptive immune memory are induced are distinct, they collude to improve host defense to pathogens. Here, we propose that innate immune memory, or "trained immunity," is a primitive form of adaptation in host defense, resulting from chromatin structure rearrangement, which provides an increased but non-specific response to reinfection. In contrast, adaptive immune memory is more advanced, with increased magnitude of response mediated through epigenetic changes, as well as specificity mediated by gene recombination. An integrative model of immune memory is important for broad understanding of host defense, and for identifying the most effective approaches to modulate it for the benefit of patients with infections and immune-mediated diseases.
            Article 0 comments Cited 176 times – based on 0 reviews     Review now
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              Rab5 and Rab7 control endocytic sorting along the axonal retrograde transport pathway.

              Katrin Deinhardt, Sara Salinas, Carole Verastegui … (2006)
              Vesicular pathways coupling the neuromuscular junction with the motor neuron soma are essential for neuronal function and survival. To characterize the organelles responsible for this long-distance crosstalk, we developed a purification strategy based on a fragment of tetanus neurotoxin (TeNT H(C)) conjugated to paramagnetic beads. This approach enabled us to identify, among other factors, the small GTPase Rab7 as a functional marker of a specific pool of axonal retrograde carriers, which transport neurotrophins and their receptors. Furthermore, Rab5 is essential for an early step in TeNT H(C) sorting but is absent from axonally transported vesicles. Our data demonstrate that TeNT H(C) uses a retrograde transport pathway shared with p75(NTR), TrkB, and BDNF, which is strictly dependent on the activities of both Rab5 and Rab7. Therefore, Rab7 plays an essential role in axonal retrograde transport by controlling a vesicular compartment implicated in neurotrophin traffic.
              Article 0 comments Cited 151 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Cells
                Journal ID (iso-abbrev): Cells
                Journal ID (publisher-id): cells
                Title: Cells
                Publisher: MDPI
                ISSN (Electronic): 2073-4409
                Publication date (Electronic): 29 April 2019
                Publication date Collection: May 2019
                Volume: 8
                Issue: 5
                Electronic Location Identifier: 396
                Affiliations
                [1 ]Centre for Immune Regulation, Department of Biosciences, University of Oslo, 0371 Oslo, Norway
                [2 ]Department of Biological and Environmental Sciences and Technologies, University of Salento, 73100 Lecce, Italy
                Author notes
                [* ]Correspondence: azzurra.margiotta@ 123456ibv.uio.no (A.M.); cecilia.bucci@ 123456unisalento.it (C.B.); Tel.: +47-2285-4565 (A.M.); +39-083-229-8900 (C.B.)
                Author information
                https://orcid.org/0000-0002-0639-4931
                https://orcid.org/0000-0002-6232-6183
                Article
                Publisher ID: cells-08-00396
                DOI: 10.3390/cells8050396
                PMC ID: 6562727
                PubMed ID: 31035701
                SO-VID: 0e554b30-38b9-4eb9-8cbf-33bead9dd73e
                Copyright © © 2019 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 09 April 2019
                Date accepted : 26 April 2019
                Categories
                Subject: Review

                Keywords: rac1,rab proteins,actin cytoskeleton,gtpase,rho proteins
                Data availability:
                Keywords: rac1, rab proteins, actin cytoskeleton, gtpase, rho proteins

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