title: Interaction of surfactant protein A with the intermediate filaments desmin and vimentin.
abstract: Surfactant protein A (SP-A), a member of the collectin family that modulates innate immunity, has recently been involved in the physiology of reproduction. Consistent with the activation of ERK-1/2 and COX-2 induced by SP-A in myometrial cells, we reported previously the presence of two major proteins recognized by SP-A in these cells. Here we identify by mass spectrometry one of these SP-A targets as the intermediate filament (IF) desmin. In myometrial preparations derived from desmin-deficient mice, the absence of binding of SP-A to any 50 kDa protein confirmed the identity of this SP-A-binding site as desmin. Our data based on partial chymotrypsin digestion of pure desmin suggested that SP-A recognizes especially its rod domain, which is known to play an important role during the assembly of desmin into filaments. In line with that, electron microscopy experiments showed that SP-A inhibits in vitro the polymerization of desmin filaments. SP-A also recognized in vitro polymerized filaments in a calcium-dependent manner at a physiological ionic strength but not the C1q receptor gC1qR. Furthermore, Texas Red-labeled SP-A colocalized with desmin filaments in myometrial cells. Interestingly, vimentin, the IF characteristic of leukocytes, is one of the major proteins recognized by SP-A in protein extracts of U937 cells after PMA-induced differentiation of this monocytic cell line. Interaction of SP-A with vimentin was further confirmed using recombinant vimentin in solid-phase binding assays. The ability of SP-A to interact with desmin and vimentin, and to prevent polymerization of desmin monomers, shed light on unexpected and wider biological roles of this collectin.
authors.affiliation: Institut de Biochimie et Biophysique Moléculaire et Cellulaire, UMR-8619 du CNRS, Université de Paris-Sud, 91400 Orsay, France. ignaciogarciaverdugo@yahoo.com
authors.forename: Ignacio
authors.initials: I
authors.lastname: Garcia-Verdugo
authors.forename: Monique
authors.initials: M
authors.lastname: Synguelakis
authors.forename: Jeril
authors.initials: J
authors.lastname: Degrouard
authors.forename: Claudio-Areias
authors.initials: CA
authors.lastname: Franco
authors.forename: Benoit
authors.initials: B
authors.lastname: Valot
authors.forename: Michel
authors.initials: M
authors.lastname: Zivy
authors.forename: Richard
authors.initials: R
authors.lastname: Chaby
authors.forename: Zahra
authors.initials: Z
authors.lastname: Tanfin
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002457:Cell Extracts; D002478:Cells, Cultured; D003893:Desmin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D007382:Intermediate Filaments / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009994:Osmolar Concentration; D011485:Protein Binding; D037662:Pulmonary Surfactant-Associated Protein A / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D053719:Tandem Mass Spectrometry; D014746:Vimentin / Q000378:metabolism*
chemical_list: D002457:Cell Extracts; D003893:Desmin; D037662:Pulmonary Surfactant-Associated Protein A; D014746:Vimentin; D002118:Calcium