Dysferlin regulates cell adhesion in human monocytes

Antoine De Morreé, Bàrbara Flix, Ivana Bagaric, Jun Wang, Marlinde Van Den Boogaard, Laure Grand Moursel, Rune R. Frants, Isabel Illa, Eduard Gallardo, Rene Toes, Silver̀e M. Van Der Maarel

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

45 Citaten (Scopus)

Samenvatting

Dysferlin is mutated in a group of muscular dystrophies commonly referred to as dysferlinopathies. It is highly expressed in skeletal muscle, where it is important for sarcolemmal maintenance. Recent studies show that dysferlin is also expressed in monocytes. Moreover, muscle of dysferlinopathy patients is characterized by massive immune cell infiltrates, and dysferlin-negative monocytes were shown to be more aggressive and phagocytose more particles. This suggests that dysferlin deregulation in monocytes might contribute to disease progression, but the molecular mechanism is unclear. Here we show that dysferlin expression is increased with differentiation in human monocytes and the THP1 monocyte cell model. Freshly isolated monocytes of dysferlinopathy patients show deregulated expression of fibronectin and fibronectin-binding integrins, which is recapitulated by transient knockdown of dysferlin in THP1 cells. Dysferlin forms a protein complex with these integrins at the cell membrane, and its depletion impairs cell adhesion. Moreover, patient macrophages show altered adhesion and motility. These findings suggest that dysferlin is involved in regulating cellular interactions and provide new insight into dysferlin function in inflammatory cells.

Originele taal-2Engels
Pagina's (van-tot)14147-14157
Aantal pagina's11
TijdschriftJournal of Biological Chemistry
Volume288
Nummer van het tijdschrift20
DOI's
StatusGepubliceerd - 17 mei 2013
Extern gepubliceerdJa

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