Browsing by Subject "Membrane traffic"

Now showing 1 - 4 of 4
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    Fragmentation of the Golgi complex of dopaminergic neurons in human substantia nigra: new cytopathological findings in Parkinson's disease
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2021) Tomás, Mónica; Martínez Martínez, Narcisa; Cara Esteban, Mireia; Martínez Alonso, Emma; Martínez Menárguez, José Ángel
    Fragmentation of the Golgi ribbon is a common feature of Parkinson's disease and other neurodegenerative diseases. This alteration could be the consequence of the anterograde and retrograde transport imbalance, α-synuclein aggregates, and/or cytoskeleton alterations. Most information on this process has been obtained from cellular and animal experimental models, and as such, there is little information available on human tissue. If the information on human tissue was available, it may help to understand the cytopathological mechanisms of this disease. In the present study, we analyzed the morphological characteristics of the Golgi complex of dopaminergic neurons in human samples of substantia nigra of control and Parkinson's disease patients. We measured the expression levels of putative molecules involved in Golgi fragmentation, including α-synuclein, tubulin, and Golgi-associated regulatory and structural proteins. We show that, as a consequence of the disease, the Golgi complex is fragmented into small stacks without vesiculation. We found that only a limited number of regulatory proteins are altered. Rab1, a small GTPase regulating endoplasmic reticulum-to-Golgi transport, is the most dramatically affected, being highly overexpressed in the surviving neurons. We found that the SNARE protein syntaxin 5 forms extracellular aggregates resembling the amyloid plaques characteristic of Alzheimer's disease. These findings may help to understand the cytopathology of Parkinson's disease.
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    How can mammalian Rab small GTPases be comprehensively analyzed?: Development of new tools to comprehensively analyze mammalian Rabs in membrane traffic
    (Murcia : F. Hernández, 2010) Fukuda, Mitsunori
    Small GTPase Rabs constitute the largest family of membrane trafficking proteins that are conserved in all eukaryotic cells. The number of different Rab isoforms in multicellular organisms is usually greater than that in unicellular organisms (e.g., approximately 60 different Rabs in each species of mammals investigated versus approximately 10 Rabs in yeasts). The expansion of Rab isoforms in mammals is often regarded as due to the acquisition of specialized membrane trafficking events in the specialized cell types of higher eukaryotes. However, because of their large numbers the precise function of most mammalian Rab isoforms is still unknown. The recent development of new tools for comprehensive analysis (e.g., Rab panels) has paved the way for systematic investigation of the involvement of mammalian Rab isoforms in specialized membrane trafficking events. The tools include collections of enhanced green fluorescent protein (EGFP)-tagged mouse and human Rabs, FLAG-tagged Rabs, glutathione S-transferase (GST)-tagged Rabs, Gal4-binding domain (GBD)-tagged Rabs, Tre- 2/Bub2/Cdc16 (TBC) domain-containing Rab-GTPaseactivating proteins (GAPs), and small interfering RNAs. EGFP-Rabs are used to screen for Rabs that are localized on specific organelles and regulate their transport, and GST-Rabs and GBD-Rabs are used to screen for novel Rab effectors by GST pull-down assays and yeast two-hybrid assays, respectively. Combined use of these tools now makes it possible to efficiently determine the function of mammalian Rab isoforms in membrane traffic. This article reviews the development of new tools for systematic analysis of Rab proteins and their application to Rab-mediated membrane traffic.
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    Rab family small GTPases-mediated regulation of intracellular logistics in neural development
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Shikanai, Mima; Yuzaki, Michisuke; Kawauchi, Takeshi
    Rab family small GTPases play essential roles in various cellular events via the regulation of intracellular logistics comprising a large number of membrane traffic pathways. Emerging evidence reveals the physiological roles of Rab proteins in several tissues, including developing brains. Many Rab proteins, such as Rab5, Rab6, Rab7, Rab8, Rab10, Rab11, Rab17 and Rab18, are shown to regulate neurite outgrowth in PC12 cells and/or axon and dendrite formation in primary cultured neurons. Recent studies have also revealed in vivo roles of several Rab family small GTPases in brain development and its related neurological disorders. In this review, we introduce the physiological function of Rab family proteins in neural development with particular focus on neurite outgrowth and neuronal migration.
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    Rab GTPases-cargo direct interactions: fine modulators of intracellular trafficking
    (F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2013) Aloisi, Ana Laura; Bucci, Cecilia
    Rab proteins are a large family of monomeric GTPases that comprise about 70 members. These proteins cycle from a GDP-bound to a GTP-bound state and are considered molecular switches of membrane traffic. Indeed, they control several steps of vesicular trafficking such as vesicle formation, vesicle movement on actin and tubulin cytoskeletal tracks, vesicle tethering, docking and fusion to the target compartment. Accordingly, Rab proteins are considered key factors in vesicular trafficking as they have a fundamental role in specifying identity and routing of vesicles and organelles. Given their role in membrane traffic, it is not surprising that Rab proteins control the cellular fate of several membrane molecules such as signal transduction receptors and ion channels, being thus fundamental for their correct function. However, much evidence of interaction of a number of Rab proteins with cargo has been reported, raising the question of the functional meaning of these interactions. Indeed, Rab proteins have been demonstrated to directly interact with several membrane proteins, such as signaling receptors, immunoglobulin receptors, integrins and ion channels. Growing evidence indicates that, through interactions with Rab proteins, cargos directly control their own fate. Furthermore, often a cargo protein has the ability to interact with more than one Rab and/or with the same Rab in different activation states. This review focuses on these interactions highlighting their role in modulating cargo’s trafficking and functions.