Articolo in rivista, 2007, ENG, 10.1172/JCI30328

Van Wesenbeeck L, Odgren PR, Coxon FP, Frattini A, Moens P, Perdu B, MacKay CA, Van Hul E, Timmermans JP, Vanhoenacker F, Jacobs R, Peruzzi B, Teti A, Helfrich MH, Rogers MJ, Villa A, Van Hul W.

Van Wesenbeeck L; Odgren PR; Coxon FP; Frattini A; Moens P; Perdu B; MacKay CA; Van Hul E; Timmermans JP; Vanhoenacker F; Jacobs R; Peruzzi B; Teti AM; Helfrich MH; Rogers MJ; Villa A; Van Hul W.

Department of Medical Genetics, University of Antwerp, Antwerp, Belgium. Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts, USA. Department of Medicine and Therapeutics, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom. Instituto Tecnologie Biomediche, Consiglio Nazionale delle Ricerche, Segrate, Italy. Pediatric Orthopaedics, Catholic University of Leuven, Leuven, Belgium. Laboratory of Cell Biology and Histology, University of Antwerp, Antwerp, Belgium. Department of Radiology, University Hospital of Antwerp, Antwerp, Belgium. Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy.

This study illustrates that Plekhm1 is an essential protein for bone resorption, as loss-of-function mutations were found to underlie the osteopetrotic phenotype of the incisors absent rat as well as an intermediate type of human osteopetrosis. Electron and confocal microscopic analysis demonstrated that monocytes from a patient homozygous for the mutation differentiated into osteoclasts normally, but when cultured on dentine discs, the osteoclasts failed to form ruffled borders and showed little evidence of bone resorption. The presence of both RUN and pleckstrin homology domains suggests that Plekhm1 may be linked to small GTPase signaling. We found that Plekhm1 colocalized with Rab7 to late endosomal/lysosomal vesicles in HEK293 and osteoclast-like cells, an effect that was dependent on the prenylation of Rab7. In conclusion, we believe PLEKHM1 to be a novel gene implicated in the development of osteopetrosis, with a putative critical function in vesicular transport in the osteoclast.

The Journal of clinical investigation 117 (4), pp. 919–930

Keywords

CNR authors

Frattini Annalisa, Villa Anna

CNR institutes

ITB – Istituto di tecnologie biomediche

ID: 183977

Year: 2007

Type: Articolo in rivista

Creation: 2012-05-02 12:01:36.000

Last update: 2022-06-13 15:52:24.000

External links

OAI-PMH: Dublin Core

OAI-PMH: Mods

OAI-PMH: RDF

DOI: 10.1172/JCI30328

URL: http://www.jci.org/

External IDs

CNR OAI-PMH: oai:it.cnr:prodotti:183977

DOI: 10.1172/JCI30328