Coronin1C Is a GDP-Specific Rab44 Effector That Controls Osteoclast Formation by Regulating Cell Motility in Macrophages

Yamaguchi, Yu; Kadowaki, Tomoko; Aibara, Nozomi; Ohyama, Kaname; Okamoto, Kuniaki; Sakai, Eiko; Tsukuba, Takayuki

doi:10.3390/ijms23126619

Cited by 5 publications

(4 citation statements)

References 42 publications

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“…An RT-PCR analysis was performed as described previously [ 32 ]. Briefly, total RNA was extracted from the tissues or cells using TRIzol reagent (Invitrogen, Carlsbad, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

Rab44 Deficiency Induces Impaired Immune Responses to Nickel Allergy

Noguromi

Yamaguchi²,

Satô³

et al. 2023

IJMS

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Rab44 was recently identified as an atypical Rab GTPase that possesses EF-hand and coiled-coil domains at the N-terminus, and a Rab-GTPase domain at the C-terminus. Rab44 is highly expressed in immune-related cells such as mast cells, macrophages, osteoclasts, and granulocyte-lineage cells in the bone marrow. Therefore, it is speculated that Rab44 is involved in the inflammation and differentiation of immune cells. However, little is known about the role of Rab44 in inflammation. In this study, we showed that Rab44 was upregulated during the early phase of differentiation of M1- and M2-type macrophages. Rab44-deficient mice exhibited impaired tumor necrosis factor alpha and interleukin-10 production after lipopolysaccharide (LPS) stimulation. The number of granulocytes in Rab44-deficient mice was lower, but the lymphocyte count in Rab44-deficient mice was significantly higher than that in wild-type mice after LPS stimulation. Moreover, Rab44-deficient macrophages showed impaired nickel-induced toxicity, and Rab44-deficient mice showed impaired nickel-induced hypersensitivity. Upon nickel hypersensitivity induction, Rab44-deficient mice showed different frequencies of immune cells in the blood and ears. Thus, it is likely that Rab44 is implicated in immune cell differentiation and inflammation, and Rab44 deficiency induces impaired immune responses to nickel allergies.

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“…An RT-PCR analysis was performed as described previously [ 32 ]. Briefly, total RNA was extracted from the tissues or cells using TRIzol reagent (Invitrogen, Carlsbad, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

Rab44 Deficiency Induces Impaired Immune Responses to Nickel Allergy

Noguromi

Yamaguchi²,

Satô³

et al. 2023

IJMS

Self Cite

View full text Add to dashboard Cite

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“…Western blot analysis was performed as previously described (Yamaguchi et al, 2022). Cells were rinsed twice with ice‐cold phosphate‐buffered saline (PBS) and lysed in cell lysis buffer (50 mM Tris‐HCl [pH 8.0], 1% Nonidet P‐40, 0.5% sodium deoxycholate, 0.1% sodium dodecyl sulfate [SDS], 150 mM NaCl, 1 mM phenylmethylsulfonyl fluoride, and proteinase inhibitor cocktail).…”

Section: Methodsmentioning

confidence: 99%

Rab44 deficiency accelerates recovery from muscle damage by regulating mTORC1 signaling and transport of fusogenic regulators

Oyakawa

Yamaguchi

Kadowaki

et al. 2023

Journal Cellular Physiology

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The skeletal muscle is a tissue that shows remarkable plasticity to adapt to various stimuli. The development and regeneration of skeletal muscles are regulated by numerous molecules. Among these, we focused on Rab44, a large Rab GTPase, that has been recently identified in immune cells and osteoclasts. Recently, bioinformatics data has revealed that Rab44 is upregulated during the myogenic differentiation of myoblasts into myotubes in C2C12 cells. Thus, Rab44 may be involved in myogenesis. Here, we have investigated the effects of Rab44 deficiency on the development and regeneration of skeletal muscle in Rab44 knockout (KO) mice. Although KO mice exhibited body and muscle weights similar to those of wild‐type (WT) mice, the histochemical analysis showed that the myofiber cross‐sectional area (CSA) of KO mice was significantly smaller than that of WT mice. Importantly, the results of muscle regeneration experiments using cardiotoxin revealed that the CSA of KO mice was significantly larger than that of WT mice, suggesting that Rab44 deficiency promotes muscle regeneration. Consistent with the in vivo results, in vitro experiments indicated that satellite cells derived from KO mice displayed enhanced proliferation and differentiation. Mechanistically, KO satellite cells exhibited an increased mechanistic target of rapamycin complex 1 (mTORC1) signaling compared to WT cells. Additionally, enhanced cell surface transport of myomaker and myomixer, which are essential membrane proteins for myoblast fusion, was observed in KO satellite cells compared to WT cells. Therefore, Rab44 deficiency enhances muscle regeneration by modulating the mTORC1 signaling pathway and transport of fusogenic regulators.

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“…The pull-down assay was performed as described previously [41]. Brie y, after washing with PBS twice, the cells were lysed in a cell lysis buffer (50 mM Tris-HCl pH 8.0, 1% Nonidet P-40, 0.5% sodium deoxycholate, 0.1% SDS, 150 mM NaCl, 1 mM PMSF, and proteinase inhibitor cocktail).…”

Section: Gtp-speci C Pull-down Assaymentioning

confidence: 99%

“…MALDI-TOF-MS was performed as described previously [41]. Samples from the pull-down assay were subjected to SDS-PAGE and Coomassie Brilliant Blue (CBB) staining.…”

Section: Matrix Associated Laser Desorption/ionization (Maldi)-time O...mentioning

confidence: 99%

Abr, a Rho-regulating protein, modulates osteoclastogenesis by enhancing lamellipodia formation by interacting with poly(ADP-ribose) glycohydrolase

et al. 2023

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Background: Osteoclasts are multinucleated bone-resorbing cells formed by the fusion of monocyte/macrophage lineage. During osteoclast differentiation, Rho GTPases are involved in various processes, including cell migration, adhesion, and polarity. However, the role of Rho-regulatory molecules in the regulation of osteoclast differentiation remains unclear. In this study, among these genes, we focused on active breakpoint cluster region-related (Abr) protein that is a multifunctional regulator of Rho GTPases.Methods and Results: We examined using knockdown and overexpression experiments in RANKLstimulated RAW-D macrophages whether Abr regulates osteoclast differentiation and cell morphology.We observed an increase in Abr expression during osteoclast differentiation and identi ed expression of a variant of the Abrgene in osteoclasts. Knockdown of Abrsuppressed osteoclast differentiation and resorption. Abr knockdown markedly inhibited the expression of osteoclast markers, such as Nfatc1, cfos, Src, and Ctsk in osteoclasts. Conversely, overexpression of Abr enhanced the formation of multinucleated osteoclasts, bone resorption activity, and osteoclast marker gene expression. Moreover, Abr overexpression accelerated lamellipodia formation and induced the formation of well-developed actin in osteoclasts. Importantly, the Abr protein interacted with poly(ADP-ribose) glycohydrolase (PARG) and Rho GTPases, including RhoA, Rac1/2/3, and Cdc42 in osteoclasts.Conclusions: Taken together, these results indicate that Abr modulates osteoclastogenesis by enhancing lamellipodia formation via its interaction with PARG.

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Coronin1C Is a GDP-Specific Rab44 Effector That Controls Osteoclast Formation by Regulating Cell Motility in Macrophages

Cited by 5 publications

References 42 publications

Rab44 Deficiency Induces Impaired Immune Responses to Nickel Allergy

Rab44 Deficiency Induces Impaired Immune Responses to Nickel Allergy

Rab44 deficiency accelerates recovery from muscle damage by regulating mTORC1 signaling and transport of fusogenic regulators

Abr, a Rho-regulating protein, modulates osteoclastogenesis by enhancing lamellipodia formation by interacting with poly(ADP-ribose) glycohydrolase

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