title: Role of calcium in membrane interactions by PI(4,5)P₂-binding proteins.
abstract: Ca²⁺ and phosphatidylinositol 4,5-bisphosphate [PI(4,5)P₂] are key agents in membrane-associated signalling events. Their temporal and spatial regulation is crucial for activation or recruitment of proteins in the plasma membrane. In fact, the interaction of several signalling proteins with PI(4,5)P₂ has been shown to be tightly regulated and dependent on the presence of Ca²⁺, with co-operative binding in some cases. In these proteins, PI(4,5)P₂ and Ca²⁺ binding typically occurs at different binding sites. In addition, several PI(4,5)P₂-binding proteins are known targets of calmodulin (CaM), which, depending on the presence of calcium, can compete with PI(4,5)P₂ for protein interaction, translating Ca²⁺ transient microdomains into variations of PI(4,5)P₂ lateral organization in time and space. The present review highlights different examples of calcium-dependent PI(4,5)P₂-binding proteins and discusses the possible impact of this dual regulation on fine-tuning of protein activity by triggering target membrane binding in the presence of subtle changes in the levels of calcium or PI(4,5)P₂.
authors.affiliation: *Centro de Química-Física Molecular and IN-Instituto de Nanociência e Nanotecnologia, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Marina E
authors.initials: ME
authors.lastname: Monteiro
authors.affiliation: *Centro de Química-Física Molecular and IN-Instituto de Nanociência e Nanotecnologia, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Sarmento
authors.affiliation: *Centro de Química-Física Molecular and IN-Instituto de Nanociência e Nanotecnologia, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Fábio
authors.initials: F
authors.lastname: Fernandes
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism; D000494:Allosteric Regulation; D000818:Animals; D017306:Annexin A2 / Q000737:chemistry / Q000378:metabolism*; D001667:Binding, Competitive; D020013:Calcium Signaling; D002147:Calmodulin / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D021962:Membrane Microdomains / Q000737:chemistry / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D051571:Protein Kinase C-alpha / Q000737:chemistry / Q000378:metabolism*; D050863:Synaptotagmin I / Q000737:chemistry / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000737:chemistry / Q000378:metabolism; D000097624:Rabphilin-3A
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D017306:Annexin A2; D002147:Calmodulin; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D019269:Phosphatidylinositol 4,5-Diphosphate; D051571:Protein Kinase C-alpha; D050863:Synaptotagmin I; D033921:Vesicular Transport Proteins; D000097624:Rabphilin-3A; C472822:ANXA2 protein, human; C494310:SYT1 protein, human; C496628:PRKCA protein, human