title: Annexins as organizers of cholesterol- and sphingomyelin-enriched membrane microdomains in Niemann-Pick type C disease.
abstract: Growing evidence suggests that membrane microdomains enriched in cholesterol and sphingomyelin are sites for numerous cellular processes, including signaling, vesicular transport, interaction with pathogens, and viral infection, etc. Recently some members of the annexin family of conserved calcium and membrane-binding proteins  have been recognized as cholesterol-interacting molecules and suggested to play a role in the formation, stabilization, and dynamics of membrane microdomains  to affect membrane lateral organization and to attract other proteins and signaling molecules onto their territory. Furthermore, annexins were implicated in the interactions between cytosolic and membrane molecules, in the turnover and storage of cholesterol  and in various signaling pathways. In this review, we focus on the mechanisms of interaction of annexins with lipid microdomains and the role of annexins in membrane microdomains dynamics including possible participation of the domain-associated forms of annexins in the etiology of human lysosomal storage disease called Niemann-Pick type C disease, related to the abnormal storage of cholesterol in the lysosome-like intracellular compartment. The involvement of annexins and cholesterol/sphingomyelin-enriched membrane microdomains in other pathologies including cardiac dysfunctions, neurodegenerative diseases, obesity, diabetes mellitus, and cancer is likely, but is not supported by substantial experimental observations, and therefore awaits further clarification.
authors.affiliation: Laboratory of Lipid Biochemistry, Department of Biochemistry, Nencki Institute of Experimental Biology, 3 Pasteur Street, 02-093, Warsaw, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Domon
authors.forename: Mehmet Nail
authors.initials: MN
authors.lastname: Nasir
authors.forename: Gladys
authors.initials: G
authors.lastname: Matar
authors.forename: Slawomir
authors.initials: S
authors.lastname: Pikula
authors.forename: Françoise
authors.initials: F
authors.lastname: Besson
authors.forename: Joanna
authors.initials: J
authors.lastname: Bandorowicz-Pikula
mesh_terms: D000595:Amino Acid Sequence; D017302:Annexins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D002784:Cholesterol / Q000378:metabolism*; D006801:Humans; D021962:Membrane Microdomains / Q000378:metabolism*; D008969:Molecular Sequence Data; D052556:Niemann-Pick Disease, Type C / Q000378:metabolism* / Q000473:pathology; D016415:Sequence Alignment; D013109:Sphingomyelins / Q000378:metabolism*
chemical_list: D017302:Annexins; D013109:Sphingomyelins; D002784:Cholesterol