title: A "mix-and-match" approach to designing Ca(2+) microdomains at membrane-contact sites.
abstract: Ca(2+) microdomains are critical for regulating cellular activity and often form at membrane contact sites. Such sites between lysosomes and the ER potentially provide a platform for signaling by the Ca(2+) mobilizing messenger NAADP. However, at present we know little of how Ca(2+) release events are coordinated at these experimentally intractable junctions. We therefore developed a computational model of lysosome-ER microdomains, which suggested that small leaks of Ca(2+) from the lysosome couple to Ca(2+)-sensitive Ins(1,4,5)P 3 receptors on the ER to generate global, microdomain-dependent Ca(2+) signals. Here we discuss how the "mix-and-match" arrangement of different Ca(2+) signaling proteins on the "source" and "target" membranes might generate functionally heterogeneous Ca(2+) microdomains.
authors: Department of Cell and Developmental Biology; University College London; London, UK.
authors: Christopher J
authors: CJ
authors: Penny
authors: Department of Cell and Developmental Biology; University College London; London, UK.
authors: Bethan S
authors: BS
authors: Kilpatrick
authors: Department of Mathematics; University of Auckland; Auckland, New Zealand.
authors: Jung
authors: J
authors: Min Han
authors: Department of Mathematics; University of Auckland; Auckland, New Zealand.
authors: James
authors: J
authors: Sneyd
authors: Department of Cell and Developmental Biology; University College London; London, UK.
authors: Sandip
authors: S
authors: Patel
keywords: 2-Pore Channel; Ca2+; Endoplasmic Reticulum; Lysosomes; Membrane Contact Sites; Microdomains; NAADP; SERCA; computational modeling