Dysferlin Regulates Cell Adhesion in Human Monocytes
Por:
de Morree, A, Flix, B, Bagaric, I, Wang, J, van den Boogaard, M, Moursel, LG, Frants, RR, Illa, I, Gallardo, E, Toes, R, van der Maarel, SM
Publicada:
17 may 2013
Resumen:
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.
Filiaciones:
de Morree, A:
Leiden Univ, Med Ctr, Dept Human Genet, NL-2333 ZA Leiden, Netherlands
Flix, B:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Lab Neurol Expt, Serv Neurol, Bellaterra 08193, Spain
Univ Autonoma Barcelona, Inst Recerca, HSCSP, Bellaterra 08193, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Bellaterra 08193, Spain
Bagaric, I:
Leiden Univ, Med Ctr, Dept Human Genet, NL-2333 ZA Leiden, Netherlands
Wang, J:
Leiden Univ, Med Ctr, Dept Rheumatol, NL-2333 ZA Leiden, Netherlands
van den Boogaard, M:
Leiden Univ, Med Ctr, Dept Human Genet, NL-2333 ZA Leiden, Netherlands
Moursel, LG:
Leiden Univ, Med Ctr, Dept Human Genet, NL-2333 ZA Leiden, Netherlands
Frants, RR:
Leiden Univ, Med Ctr, Dept Human Genet, NL-2333 ZA Leiden, Netherlands
Illa, I:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Lab Neurol Expt, Serv Neurol, Bellaterra 08193, Spain
Univ Autonoma Barcelona, Inst Recerca, HSCSP, Bellaterra 08193, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Bellaterra 08193, Spain
Gallardo, E:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Lab Neurol Expt, Serv Neurol, Bellaterra 08193, Spain
Univ Autonoma Barcelona, Inst Recerca, HSCSP, Bellaterra 08193, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Bellaterra 08193, Spain
Toes, R:
Leiden Univ, Med Ctr, Dept Rheumatol, NL-2333 ZA Leiden, Netherlands
van der Maarel, SM:
Leiden Univ, Med Ctr, Dept Human Genet, NL-2333 ZA Leiden, Netherlands
Green Published, Hybrid Gold
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