In Vitro and in Vivo Characterization of Molecular Interactions between Calmodulin, Ezrin/Radixin/Moesin, and L-selectin.
J Biol Chem
; 284(13): 8833-45, 2009 Mar 27.
Article
en En
| MEDLINE
| ID: mdl-19129194
ABSTRACT
L-selectin is a cell adhesion molecule that tethers leukocytes to the luminal walls of venules during inflammation and enables them to roll under the force of blood flow. Clustering of L-selectin during rolling is thought to promote outside-in signals that lead to integrin activation and chemokine receptor expression, ultimately contributing to leukocyte arrest. Several studies have underscored the importance of the L-selectin cytoplasmic tail in functionally regulating adhesion and signaling. Interestingly, the L-selectin tail comprises only 17 amino acids, and yet it is thought to bind simultaneously to several proteins. For example, constitutive association of calmodulin (CaM) and ezrin/radixin/moesin (ERM) to L-selectin confers resistance to proteolysis and microvillar positioning, respectively. In this report we found that recombinant purified CaM and ERM bound non-competitively to the same tail of L-selectin. Furthermore, molecular modeling supported the possibility that CaM, L-selectin, and moesin could form a heterotrimeric complex. Finally, using fluorescence lifetime imaging microscopy to measure fluorescence resonance energy transfer, it was shown that CaM, L-selectin, and ERM could interact simultaneously in vivo. Moreover, L-selectin clustering promoted CaM/ERM interaction in cis (i.e. derived from neighboring L-selectin tails). These results highlight a novel intracellular event that occurs as a consequence of L-selectin clustering, which could participate in transducing signals that promote the transition from rolling to arrest.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Calmodulina
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Transducción de Señal
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Selectina L
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Proteínas del Citoesqueleto
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Rodamiento de Leucocito
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Complejos Multiproteicos
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Proteínas de la Membrana
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Proteínas de Microfilamentos
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Biol Chem
Año:
2009
Tipo del documento:
Article