Polyphosphoinositide binding domains: Key to inositol lipid biology.
Polyphosphoinositides (PPIn) are an important family of phospholipids located on the cytoplasmic leaflet of eukaryotic cell membranes. Collectively, they are critical for the regulation of many aspects of membrane homeostasis and signaling, with notable relevance to human physiology and disease. This regulation is achieved through the selective interaction of these lipids with hundreds of cellular proteins, and thus the capability to study these localized interactions is crucial to understanding their functions. In this review, we discuss current knowledge of the principle types of PPIn-protein interactions, focusing on specific lipid-binding domains. We then discuss how these domains have been re-tasked by biologists as molecular probes for these lipids in living cells. Finally, we describe how the knowledge gained with these probes, when combined with other techniques, has led to the current view of the lipids' localization and function in eukaryotes, focusing mainly on animal cells. This article is part of a Special Issue entitled Phosphoinositides.
Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. ghammond@pitt.edu
Gerald R V
GR
Hammond
Section on Molecular Signal Transduction, Eunice Shriver Kennedy National Institute for Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA. Electronic address: ballat@mail.nih.gov.
Tamas
T
Balla
D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015374:Biosensing Techniques; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D057054:Molecular Imaging; D015335:Molecular Probes / Q000737:chemistry* / Q000378:metabolism; D010716:Phosphatidylinositols / Q000032:analysis* / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D022021:Tacrolimus Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010738:Type C Phospholipases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C572072:FGD5 protein, human; D020662:Guanine Nucleotide Exchange Factors; D015335:Molecular Probes; C487037:PLEKHA3 protein, human; D010716:Phosphatidylinositols; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D010738:Type C Phospholipases; D022021:Tacrolimus Binding Proteins
Fluorescence imaging; Membrane; PH-domain; PX-domain; Phosphoinositide; Phospholipase C