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Spectrin functions upstream of ankyrin in a spectrin cytoskeleton assembly pathway

Journal Article · · Journal of Cell Biology
 [1];  [2];  [2];  [2]
  1. Univ. of Chicago, IL (United States). Program in Cell & Developmental Biology. Dept. of Biological Sciences; DOE/OSTI
  2. Univ. of Chicago, IL (United States). Program in Cell & Developmental Biology. Dept. of Biological Sciences
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Prevailing models place spectrin downstream of ankyrin in a pathway of assembly and function in polarized cells. We used a transgene rescue strategy in Drosophila melanogaster to test contributions of four specific functional sites in β spectrin to its assembly and function. (1) Removal of the pleckstrin homology domain blocked polarized spectrin assembly in midgut epithelial cells and was usually lethal. (2) A point mutation in the tetramer formation site, modeled after a hereditary elliptocytosis mutation in human erythrocyte spectrin, had no detectable effect on function. (3) Replacement of repetitive segments 4–11 of β spectrin with repeats 2–9 of α spectrin abolished function but did not prevent polarized assembly. (4) Removal of the putative ankyrin-binding site had an unexpectedly mild phenotype with no detectable effect on spectrin targeting to the plasma membrane. The results suggest an alternate pathway in which spectrin directs ankyrin assembly and in which some important functions of spectrin are independent of ankyrin.
Research Organization:
Univ. of Illinois, Chicago, IL (United States)
Sponsoring Organization:
National Institutes of Health (NIH); USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
OSTI ID:
1625137
Journal Information:
Journal of Cell Biology, Journal Name: Journal of Cell Biology Journal Issue: 2 Vol. 175; ISSN 0021-9525
Publisher:
Rockefeller University PressCopyright Statement
Country of Publication:
United States
Language:
English

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Cited By (9)

βIV spectrin is recruited to axon initial segments and nodes of Ranvier by ankyrinG journal February 2007
Ankyrin-G palmitoylation and βII-spectrin binding to phosphoinositide lipids drive lateral membrane assembly journal July 2014
Transgene Rescue Identifies an Essential Function for Drosophila β Spectrin in the Nervous System and a Selective Requirement for Ankyrin-2–binding Activity journal August 2010
Ankyrin protein networks in membrane formation and stabilization journal November 2009
The Plasma Membrane Potential and the Organization of the Actin Cytoskeleton of Epithelial Cells journal January 2012
Regulatory polymorphisms in the bovine Ankyrin 1 gene promoter are associated with tenderness and intramuscular fat content journal December 2010
The Drosophila Anion Exchanger (DAE) lacks a detectable interaction with the spectrin cytoskeleton journal June 2010
Key Amino Acid Residues of Ankyrin-Sensitive Phosphatidylethanolamine/Phosphatidylcholine-Lipid Binding Site of βI-Spectrin journal June 2011
Spectrin Tetramer Formation Is Not Required for Viable Development in Drosophila journal January 2015

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