Rab GTPases in Osteoclastic Endomembrane Systems

Roy, Michèle; Roux, Sophie

doi:10.1155/2018/4541538

Cited by 13 publications

(11 citation statements)

References 128 publications

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“…Other abbreviations: Beclin1: BCL-2 interacting myosin/moesin-like coiled-coil protein 1; LC3: light chain 3 [Atg8 (yeast) is called LC3 in mammals]; PtdIns3P: phosphatidylinositol 3-phosphate; SNAREs: N-ethylmaleimide-sensitive factor attachment protein receptors; WIPI: WD repeat domain phosphoinositide-interacting protein. Adapted from [ 14 ].…”

Section: Figurementioning

confidence: 99%

Rab GTPases in Osteoclastic Bone Resorption and Autophagy

Roy

Roux

2020

IJMS

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Small guanosine triphosphate hydrolases (GTPases) of the Rab family are involved in plasma membrane delivery, fusion events, and lysosomal and autophagic degradation pathways, thereby regulating signaling pathways and cell differentiation and function. Osteoclasts are bone-resorbing cells that maintain bone homeostasis. Polarized vesicular trafficking pathways result in the formation of the ruffled border, the osteoclast’s resorptive organelle, which also assists in transcytosis. Here, we reviewed the different roles of Rab GTPases in the endomembrane machinery of osteoclasts and in bone diseases caused by the dysfunction of these proteins, with a particular focus on autophagy and bone resorption. Understanding the molecular mechanisms underlying osteoclast-related bone disease development is critical for developing and improving therapies.

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Section: Figurementioning

confidence: 99%

Rab GTPases in Osteoclastic Bone Resorption and Autophagy

Roy

Roux

2020

IJMS

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“…In recent years, the importance of the autophagy (i.e. macroautophagy) during osteoclastic bone resorption and skeletal disease has been increasingly appreciated [28–30]. Indeed, several key components of the autophagic conjugation cascade (including ATG5, ATG7, ATG4B, LC3 and PLEKHM1) have been implicated in osteoclast secretory action and the maturation of the RB during bone resorption [12].…”

Section: Autophagy In Osteoclastsmentioning

confidence: 99%

Membrane trafficking in osteoclasts and implications for osteoporosis

Ribet

Pavlos

2019

Biochemical Society Transactions

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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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“…The plasma membrane in contact with the bone surface enlarges into the ruffled border that induces polarization of the osteoclast. Following this attachment, the osteoclast secretory lysosomes, also found in immune cells and melanocytes [ 12 , 13 ], will associate and move along the microtubules, fuse to the plasma membrane, and then participate in ruffled border formation [ 14 , 15 ]. The ruffled border is an infolded finger-like distortion of the plasma membrane adjacent to the bone surface that participates with lysosomal proton pump H + /V-ATPase and chloride exchanger ClC-7 in acidification of the extracellular resorbing lacunae to ensure bone matrix demineralization [ 16 , 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Ostm1 from Mouse to Human: Insights into Osteoclast Maturation

Vacher

Bruccoleri

Pata

2020

IJMS

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The maintenance of bone mass is a dynamic process that requires a strict balance between bone formation and resorption. Bone formation is controlled by osteoblasts, while osteoclasts are responsible for resorption of the bone matrix. The opposite functions of these cell types have to be tightly regulated not only during normal bone development, but also during adult life, to maintain serum calcium homeostasis and sustain bone integrity to prevent bone fractures. Disruption of the control of bone synthesis or resorption can lead to an over accumulation of bone tissue in osteopetrosis or conversely to a net depletion of the bone mass in osteoporosis. Moreover, high levels of bone resorption with focal bone formation can cause Paget’s disease. Here, we summarize the steps toward isolation and characterization of the osteopetrosis associated trans-membrane protein 1 (Ostm1) gene and protein, essential for proper osteoclast maturation, and responsible when mutated for the most severe form of osteopetrosis in mice and humans.

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Rab GTPases in Osteoclastic Endomembrane Systems

Cited by 13 publications

References 128 publications

Rab GTPases in Osteoclastic Bone Resorption and Autophagy

Rab GTPases in Osteoclastic Bone Resorption and Autophagy

Membrane trafficking in osteoclasts and implications for osteoporosis

Ostm1 from Mouse to Human: Insights into Osteoclast Maturation

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