Elucidating the contribution of osteoclast lysosomal proteins in skeletal homeostasis

Amy Ribet

doi:10.26182/q16z-a574

Elucidating the contribution of osteoclast lysosomal proteins in skeletal homeostasis

Amy Ribet

Research output: Thesis › Doctoral Thesis

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Abstract

Osteoclasts harbor specialized lysosome-related organelles essential for bone resorption termed secretory lysosomes (SL). The hybrid organelle is an acidified compartments that serve as a membrane precursor to the ruffled border, the osteoclast’s ‘resorptive apparatus’. Yet, the molecular composition of SLs remains incompletely understood. Therefore, a reproducible and scalable method was devised to isolate SLs from osteoclasts. By combining organelle-resolution proteomics and bioinformatic analyses, the molecular constituents of osteoclast SLs were curated into an organelle proteome from which new candidates involved in the regulation of bone, osteoclast, and lysosome homeostasis were selected for genetic ablation studies in vivo and in vitro.

Original language	English
Qualification	Doctor of Philosophy
Awarding Institution	The University of Western Australia
Supervisors/Advisors	Abudulai, Laila, Supervisor Ng, Pei Ying, Supervisor Pixley, Fiona, Supervisor Pavlos, Nathan, Supervisor
Thesis sponsors	Australian Government Research Training Program
Award date	20 Jul 2023
DOIs	https://doi.org/10.26182/q16z-a574
Publication status	Unpublished - 2023

Embargo information

Embargoed from 19/07/2023 to 31/07/2025. Made publicly available on 31/07/2025.

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10.26182/q16z-a574

THESIS - DOCTOR OF PHILOSOPHY - RIBET Amy Brigitte Patricia - 2023
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Sugar transporter Slc37a2 regulates bone metabolism in mice via a tubular lysosomal network in osteoclasts
Ng, P. Y., Ribet, A. B. P., Guo, Q., Mullin, B. H., Tan, J. W. Y., Landao-Bassonga, E., Stephens, S., Chen, K., Yuan, J., Abudulai, L., Bollen, M., Nguyen, E. T. T. T., Kular, J., Papadimitriou, J. M., Søe, K., Teasdale, R. D., Xu, J., Parton, R. G., Takayanagi, H. & Pavlos, N. J., Dec 2023, In: Nature Communications. 14, 1, 23 p., 906.
Research output: Contribution to journal › Article › peer-review

Open Access
24 Link opens in a new tab Citations (Scopus)
Membrane Transport Proteins in Osteoclasts: The Ins and Outs
Ribet, A. B. P., Ng, P. Y. & Pavlos, N. J., 26 Feb 2021, In: Frontiers in Cell and Developmental Biology. 9, 644986.
Research output: Contribution to journal › Review article › peer-review

Open Access
35 Link opens in a new tab Citations (Web of Science)

Cite this

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title = "Elucidating the contribution of osteoclast lysosomal proteins in skeletal homeostasis",

abstract = "Osteoclasts harbor specialized lysosome-related organelles essential for bone resorption termed secretory lysosomes (SL). The hybrid organelle is an acidified compartments that serve as a membrane precursor to the ruffled border, the osteoclast{\textquoteright}s {\textquoteleft}resorptive apparatus{\textquoteright}. Yet, the molecular composition of SLs remains incompletely understood. Therefore, a reproducible and scalable method was devised to isolate SLs from osteoclasts. By combining organelle-resolution proteomics and bioinformatic analyses, the molecular constituents of osteoclast SLs were curated into an organelle proteome from which new candidates involved in the regulation of bone, osteoclast, and lysosome homeostasis were selected for genetic ablation studies in vivo and in vitro.",

keywords = "osteoclast, bone, skeleton, lysosome, secretory lysosome, Slc37a2, Mfsd12, Membrane transport proteins",

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language = "English",

school = "The University of Western Australia",

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N2 - Osteoclasts harbor specialized lysosome-related organelles essential for bone resorption termed secretory lysosomes (SL). The hybrid organelle is an acidified compartments that serve as a membrane precursor to the ruffled border, the osteoclast’s ‘resorptive apparatus’. Yet, the molecular composition of SLs remains incompletely understood. Therefore, a reproducible and scalable method was devised to isolate SLs from osteoclasts. By combining organelle-resolution proteomics and bioinformatic analyses, the molecular constituents of osteoclast SLs were curated into an organelle proteome from which new candidates involved in the regulation of bone, osteoclast, and lysosome homeostasis were selected for genetic ablation studies in vivo and in vitro.

AB - Osteoclasts harbor specialized lysosome-related organelles essential for bone resorption termed secretory lysosomes (SL). The hybrid organelle is an acidified compartments that serve as a membrane precursor to the ruffled border, the osteoclast’s ‘resorptive apparatus’. Yet, the molecular composition of SLs remains incompletely understood. Therefore, a reproducible and scalable method was devised to isolate SLs from osteoclasts. By combining organelle-resolution proteomics and bioinformatic analyses, the molecular constituents of osteoclast SLs were curated into an organelle proteome from which new candidates involved in the regulation of bone, osteoclast, and lysosome homeostasis were selected for genetic ablation studies in vivo and in vitro.

KW - osteoclast

KW - bone

KW - skeleton

KW - lysosome

KW - secretory lysosome

KW - Slc37a2

KW - Mfsd12

KW - Membrane transport proteins

U2 - 10.26182/q16z-a574

DO - 10.26182/q16z-a574

M3 - Doctoral Thesis

ER -

Elucidating the contribution of osteoclast lysosomal proteins in skeletal homeostasis

Abstract

Embargo information

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Research output

Sugar transporter Slc37a2 regulates bone metabolism in mice via a tubular lysosomal network in osteoclasts

Membrane Transport Proteins in Osteoclasts: The Ins and Outs

Cite this