PXD023578

PXD023578 is an original dataset announced via ProteomeXchange.

Title	ELMO1 signaling is a promoter of osteoclast function and bone loss
Description	Osteoporosis and bone fractures affect millions of men and women worldwide and are often due to increased bone resorption (bone loss) mediated by osteoclasts. Here, we identify a novel role for the cytoplasmic protein ELMO1 as an important ‘signaling node’ controlling the bone resorption function of osteoclasts. Initially, we noted association of ELMO1 SNPs with bone abnormalities and altered bone density in humans. Experimentally, ELMO1 emerged as a promoter of bone loss wherein deletion of ELMO1 reversed osteoporosis / bone erosions in four in vivo mouse models: osteoprotegerin deficiency, ovariectomy, and two types of inflammatory arthritis. However, ELMO1 did not promote bone loss under homeostatic conditions. Mechanistic studies pointed to a larger ELMO1 signaling network that regulates osteoclast activity at several levels. First, transcriptomics coupled with CRISPR/Cas9 genetic deletion approaches identified new regulators of osteoclast function associated with Elmo1. Second, defining the ‘ELMO1 interactome’ in osteoclasts via proteomics revealed proteins linked to bone degradation. Third, ELMO1 affects the formation of the actin ring /sealing zone on bone-like surfaces and the distribution of osteoclast-specific proteases. Finally, a 3D structure-based inhibitory peptide targeting a highly conserved region of ELMO1 reduced bone resorption in wild type osteoclasts. Collectively, these data identify ELMO1 as a signaling hub that regulates osteoclast function and bone loss, with relevance to diseases such as osteoporosis and arthritis.
HostingRepository	PRIDE
AnnounceDate	2021-06-07
AnnouncementXML	Submission_2021-08-26_06:25:18.580.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Thomas Conrads
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-01-14 00:17:47	ID requested
1	2021-06-07 07:24:12	announced
⏵ 2	2021-08-26 06:25:19	announced	2021-08-26: Updated publication reference for PubMed record(s): 34404802.

Arandjelovic S, Perry JSA, Zhou M, Ceroi A, Smirnov I, Walk SF, Shankman LS, Cambr, é I, Onengut-Gumuscu S, Elewaut D, Conrads TP, Ravichandran KS, ELMO1 signaling is a promoter of osteoclast function and bone loss. Nat Commun, 12(1):4974(2021) [pubmed]

submitter keyword: ELMO1, Osteoclasts, bone loss, GeLC-MS

Dr. Thomas P. Conrads
contact affiliation	Women’s Health Integrated Research Center Inova Women’s Service Line Inova Health System 3289 Woodburn Rd, Annandale, VA 22042, USA
contact email	conrads@whirc.org
lab head
Thomas Conrads
contact affiliation	Inova Health System
contact email	conrads@whirc.org
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD023578
     1. Label: PRIDE project
     2. Name: ELMO1 signaling is a promoter of osteoclast function and bone loss