scholarly journals Ypt/Rab GTPases and Intracellular Membrane Trafficking: An Overview

2012 ◽  
pp. 3-17 ◽  
Keyword(s):  
Membrane Trafficking ◽  
Rab Gtpases ◽  
Intracellular Membrane

scholarly journals Rab GTPases: Central Coordinators of Membrane Trafficking in Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Hongyuan Jin ◽  
Yuanxin Tang ◽  
Liang Yang ◽  
Xueqiang Peng ◽  
Bowen Li ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Membrane Transport ◽  
Membrane Trafficking ◽  
Membrane Vesicle ◽  
Clinical Implications ◽  
Rab Gtpases ◽  
Intracellular Membrane ◽  
Cellular Functions ◽  
Vesicle Movement

Tumor progression involves invasion, migration, metabolism, autophagy, exosome secretion, and drug resistance. Cargos transported by membrane vesicle trafficking underlie all of these processes. Rab GTPases, which, through coordinated and dynamic intracellular membrane trafficking alongside cytoskeletal pathways, determine the maintenance of homeostasis and a series of cellular functions. The mechanism of vesicle movement regulated by Rab GTPases plays essential roles in cancers. Therefore, targeting Rab GTPases to adjust membrane trafficking has the potential to become a novel way to adjust cancer treatment. In this review, we describe the characteristics of Rab GTPases; in particular, we discuss the role of their activation in the regulation of membrane transport and provide examples of Rab GTPases regulating membrane transport in tumor progression. Finally, we discuss the clinical implications and the potential as a cancer therapeutic target of Rab GTPases.

scholarly journals Rab GTPases: Switching to Human Diseases

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 909 ◽  
Author(s):  
Noemi Antonella Guadagno ◽  
Cinzia Progida
Keyword(s):  
Membrane Trafficking ◽  
Intracellular Transport ◽  
Small Gtpases ◽  
Regulatory Proteins ◽  
Human Diseases ◽  
Rab Proteins ◽  
Rab Gtpases ◽  
Intracellular Membrane ◽  
And Migration ◽  
And Control

Rab proteins compose the largest family of small GTPases and control the different steps of intracellular membrane traffic. More recently, they have been shown to also regulate cell signaling, division, survival, and migration. The regulation of these processes generally occurs through recruitment of effectors and regulatory proteins, which control the association of Rab proteins to membranes and their activation state. Alterations in Rab proteins and their effectors are associated with multiple human diseases, including neurodegeneration, cancer, and infections. This review provides an overview of how the dysregulation of Rab-mediated functions and membrane trafficking contributes to these disorders. Understanding the altered dynamics of Rabs and intracellular transport defects might thus shed new light on potential therapeutic strategies.

scholarly journals Rab GTPases in Parkinson’s disease: a primer

2021 ◽  
Author(s):  
Antonio Jesús Lara Ordóñez ◽  
Rachel Fasiczka ◽  
Yahaira Naaldijk ◽  
Sabine Hilfiker
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Membrane Trafficking ◽  
Protein Function ◽  
Current Knowledge ◽  
Rab Gtpases ◽  
Intracellular Membrane ◽  
Master Regulators ◽  
Rab Protein ◽  
Physiological Properties

Abstract Parkinson’s disease is a prominent and debilitating movement disorder characterized by the death of vulnerable neurons which share a set of structural and physiological properties. Over the recent years, increasing evidence indicates that Rab GTPases can directly as well as indirectly contribute to the cellular alterations leading to PD. Rab GTPases are master regulators of intracellular membrane trafficking events, and alterations in certain membrane trafficking steps can be particularly disruptive to vulnerable neurons. Here, we describe current knowledge on the direct links between altered Rab protein function and PD pathomechanisms.

Optogenetic oligomerization of Rab GTPases regulates intracellular membrane trafficking

2016 ◽  
Vol 12 (6) ◽  
pp. 431-436 ◽  
Author(s):  
Mai Khanh Nguyen ◽  
Cha Yeon Kim ◽  
Jin Man Kim ◽  
Byung Ouk Park ◽  
Sangkyu Lee ◽  
...  
Keyword(s):  
Membrane Trafficking ◽  
Rab Gtpases ◽  
Intracellular Membrane

LRRK2 and Rab GTPases

2018 ◽  
Vol 46 (6) ◽  
pp. 1707-1712 ◽  
Author(s):  
Suzanne R. Pfeffer
Keyword(s):  
Membrane Trafficking ◽  
Protein Function ◽  
Short Review ◽  
Rab Gtpase ◽  
Rab Gtpases ◽  
Rab Protein ◽  
Complex Interactions ◽  
Preferential Binding ◽  
Bona Fide ◽  
Mutant Lrrk2

Leucine-rich repeat kinase 2 (LRRK2) is mutated in familial Parkinson's disease, and pathogenic mutations activate the kinase activity. A tour de force screen by Mann and Alessi and co-workers identified a subset of Rab GTPases as bona fide LRRK2 substrates. Rab GTPases are master regulators of membrane trafficking and this short review will summarize what we know about the connection between LRRK2 and this family of regulatory proteins. While, in most cases, Rab GTPase phosphorylation is predicted to interfere with Rab protein function, the discovery of proteins that show preferential binding to phosphorylated Rabs suggests that more complex interactions may also contribute to mutant LRRK2-mediated pathology.

scholarly journals Components of the endocytic and recycling trafficking pathways interfere with the integrity of the Legionella-containing vacuole

2019 ◽  
Author(s):  
Ila S. Anand ◽  
Won Young Choi ◽  
Ralph R. Isberg
Keyword(s):  
Membrane Trafficking ◽  
Legionella Pneumophila ◽  
Host Cells ◽  
Rab Gtpases ◽  
Intracellular Growth ◽  
Mutant Proteins ◽  
Host Cytoplasm ◽  
Downstream Effectors ◽  
Cell Death Response ◽  
Host Membrane

SummaryLegionella pneumophila requires the Dot/Icm translocation system to replicate in a vacuolar compartment within host cells. Strains lacking the translocated substrate SdhA form a permeable vacuole during residence in the host cell, exposing bacteria to the host cytoplasm. In primary macrophages, mutants are defective for intracellular growth, with a pyroptotic cell death response mounted due to bacterial exposure to the cytosol. To understand how SdhA maintains vacuole integrity during intracellular growth, we performed high-throughput RNAi screens against host membrane trafficking genes to identify factors that antagonize vacuole integrity in the absence of SdhA. Depletion of host proteins involved in endocytic uptake and recycling resulted in enhanced intracellular growth and lower levels of permeable vacuoles surrounding the ΔsdhA mutant. Of interest were three different Rab GTPases involved in these processes: Rab11b, Rab8b and Rab5 isoforms, that when depleted resulted in enhanced vacuole integrity surrounding the sdhA mutant. Proteins regulated by these Rabs are responsible for interfering with proper vacuole membrane maintenance, as depletion of the downstream effectors EEA1, Rab11FIP1, or VAMP3 rescued vacuole integrity and intracellular growth of the sdhA mutant. To test the model that specific vesicular components associated with these effectors could act to destabilize the replication vacuole, EEA1 and Rab11FIP1 showed enhanced colocalization with the vacuole surrounding the sdhA mutant compared with the WT vacuole. Depletion of Rab5 isoforms or Rab11b reduced this aberrant colocalization. These findings are consistent with SdhA interfering with both endocytic and recycling membrane trafficking events that act to destabilize vacuole integrity during infection.

scholarly journals Mammalian PITPs at the Golgi and ER-Golgi Membrane Contact Sites

Contact ◽  
2020 ◽  
Vol 3 ◽  
pp. 251525642096417
Author(s):  
Shamshad Cockcroft ◽  
Sima Lev
Keyword(s):  
Membrane Trafficking ◽  
Golgi Membrane ◽  
Intracellular Membrane ◽  
Functional Studies ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Biochemical Genetic ◽  
Membrane Contact ◽  
Intracellular Membrane Transport ◽  
Exchange Activity

Phosphatidylinositol (PI)-transfer proteins (PITPs) have been long recognized as proteins that modulate phosphoinositide levels in membranes through their intrinsic PI/PC-exchange activity. Recent studies from flies and mammals suggest that certain PITPs bind phosphatidic acid (PA) and possess PI/PA-exchange activity. Phosphoinositides and PA play critical roles in cell signaling and membrane trafficking, and numerous biochemical, genetic and functional studies have shown that PITPs regulate cellular lipid metabolism, various signaling pathways and intracellular membrane transport events. In this mini-review, we discuss the function of mammalian PITPs at the Golgi and ER-Golgi membrane contact sites (MCS) and highlight DAG (Diacylglycerol) as a central hub of PITPs functions. We describe PITPs-associated phospho-signaling network at the ER-Golgi interface, and share our perspective on future studies related to PITPs at MCSs.

scholarly journals Membrane trafficking in osteoclasts and implications for osteoporosis

2019 ◽  
Vol 47 (2) ◽  
pp. 639-650 ◽  
Author(s):  
Pei Ying Ng ◽  
Amy Brigitte Patricia Ribet ◽  
Nathan John Pavlos
Keyword(s):  
Membrane Trafficking ◽  
Bone Matrix ◽  
Rab Gtpases ◽  
Sorting Nexin ◽  
Multinucleated Cells ◽  
Biological Studies ◽  
Endocytic Sorting ◽  
Molecular Machinery ◽  
Intracellular Organelles ◽  
Ruffled Border

Abstract Osteoclasts are large multinucleated cells exquisitely adapted to resorb bone matrix. Like other eukaryotes, osteoclasts possess an elaborate ensemble of intracellular organelles through which solutes, proteins and other macromolecules are trafficked to their target destinations via membrane-bound intermediaries. During bone resorption, membrane trafficking must be tightly regulated to sustain the structural and functional polarity of the osteoclasts’ membrane domains. Of these, the ruffled border (RB) is most characteristic, functioning as the osteoclasts' secretory apparatus. This highly convoluted organelle is classically considered to be formed by the targeted fusion of acidic vesicles with the bone-facing plasma membrane. Emerging findings disclose new evidence that the RB is far more complex than previously envisaged, possessing discrete subdomains that are serviced by several intersecting endocytic, secretory, transcytotic and autophagic pathways. Bone-resorbing osteoclasts therefore serve as a unique model system for studying polarized membrane trafficking. Recent advances in high-resolution microscopy together with the convergence of genetic and cell biological studies in humans and in mice have helped illuminate the major membrane trafficking pathways in osteoclasts and unmask the core molecular machinery that governs these distinct vesicle transport routes. Among these, small Rab GTPases, their binding partners and members of the endocytic sorting nexin family have emerged as critical regulators. This mini review summarizes our current understanding of membrane trafficking in osteoclasts, the key molecular participants, and discusses how these transport machinery may be exploited for the development of new therapies for metabolic disorders of bone-like osteoporosis.

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