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 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
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
CNR authors
CNR institutes
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