Calmodulin interacts with Rab3D and modulates osteoclastic bone resorption

Sipin Zhu, Shek Man Chim, Taksum Cheng, Estabelle Ang, Benjamin Ng, Baysie Lim, Kai Chen, Heng Qiu, Jennifer Tickner, H. Xu, Nathan Pavlos, Jiake Xu

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Calmodulin is a highly versatile protein that regulates intracellular calcium homeostasis and is involved in a variety of cellular functions including cardiac excitability, synaptic plasticity and signaling transduction. During osteoclastic bone resorption, calmodulin has been reported to concentrate at the ruffled border membrane of osteoclasts where it is thought to modulate bone resorption activity in response to calcium. Here we report an interaction between calmodulin and Rab3D, a small exocytic GTPase and established regulator osteoclastic bone resorption. Using yeast two-hybrid screening together with a series of protein-protein interaction studies, we show that calmodulin interacts with Rab3D in a calcium dependent manner. Consistently, expression of a calcium insensitive form of calmodulin (i.e. CaM1234) perturbs calmodulin-Rab3D interaction as monitored by bioluminescence resonance energy transfer (BRET) assays. In osteoclasts, calmodulin and Rab3D are constitutively co-expressed during RANKL-induced osteoclast differentiation, co-occupy plasma membrane fractions by differential gradient sedimentation assay and colocalise in the ruffled border as revealed by confocal microscopy. Further, functional blockade of calmodulin-Rab3D interaction by calmidazolium chloride coincides with an attenuation of osteoclastic bone resorption. Our data imply that calmodulin- Rab3D interaction is required for efficient bone resorption by osteoclasts in vitro.
Original languageEnglish
Pages (from-to)1-9
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 29 Nov 2016

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Calmodulin
Bone Resorption
Osteoclasts
Calcium
calmidazolium
Proteins
Neuronal Plasticity
Monomeric GTP-Binding Proteins
Energy Transfer
Confocal Microscopy
Homeostasis
Yeasts
Cell Membrane
Membranes

Cite this

Zhu, Sipin ; Chim, Shek Man ; Cheng, Taksum ; Ang, Estabelle ; Ng, Benjamin ; Lim, Baysie ; Chen, Kai ; Qiu, Heng ; Tickner, Jennifer ; Xu, H. ; Pavlos, Nathan ; Xu, Jiake. / Calmodulin interacts with Rab3D and modulates osteoclastic bone resorption. In: Scientific Reports. 2016 ; Vol. 6. pp. 1-9.
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Calmodulin interacts with Rab3D and modulates osteoclastic bone resorption. / Zhu, Sipin; Chim, Shek Man; Cheng, Taksum; Ang, Estabelle; Ng, Benjamin; Lim, Baysie; Chen, Kai; Qiu, Heng; Tickner, Jennifer; Xu, H.; Pavlos, Nathan; Xu, Jiake.

In: Scientific Reports, Vol. 6, 29.11.2016, p. 1-9.

Research output: Contribution to journalArticle

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AU - Zhu, Sipin

AU - Chim, Shek Man

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AU - Ang, Estabelle

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AU - Lim, Baysie

AU - Chen, Kai

AU - Qiu, Heng

AU - Tickner, Jennifer

AU - Xu, H.

AU - Pavlos, Nathan

AU - Xu, Jiake

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