spectrins its structure,function and role in animal cells
TRANSCRIPT
Spectrins its structure,functionand role in animal
cells
INTRODUcTION
• Spectrin is a cytoskeletal protein.
• First isolated as a major protein component of human red blood cells.
• Forms pentagonal or hexagonal arrangements, playing an important role in maintenance of plasma membrane integrity and cytoskeletal structure.
Spectrins: several genes and numerous isoforms widelydistributed in all metazoan cells
• Exist mainly as heterotetramersmade of various a and b subunit isoforms.
• SPTA1 and SPTAN,SPTB,SPTBN1, SPTBN2, SPTBN4 & SPTBN5
• C.elegans and D.melanogaster-a-spectrin bG & bH-spectrin.
• a-Spectrins contain 20 spectrinrepeats, b-spectrins are made of 17 spectrin repeats (b1-b17), while the heavy bV-spectrins contain 30 repeats.
• Ankyrin, 4.1 complex-which includes actin, dematin,adducin, tropomyosin and tropomodulin, glycophorin C.
Spectrins are a structural platform for stabilizationand activation of membrane microdomains
• Spectrin-based skeleton participates in the organization of specialized membranes.
• No accumulation of membrane partners at the appropriate site within the membrane.
• Spinocerebellar ataxia type 5 (SCA5) and neurodegenerative disease.
• Tremors and contraction of the hindlimbs-mice.
• Loss of Na+K+ ATPase from the basolateral domain of epithelial cells- Drosophila.
Spectrins are multifunctional proteins involvedin regulation of cell morphology and mechanical
properties
• Hereditary hemolytic anemia associated with mutations in both aI- and bI-spectrins.
• In epithelial cells, knockdown of bII-spectrin results in loss of the lateral membrane, expansion of the apical and basal membrane area, and conversion of cells from columnar to squamousmorphology.
• a- and b-spectrins are required during nervous system development-NCAM.
Spectrins, cell cycle and DNA repair
• The presence of spectrin in a complex including TGFb-R1-Beckwith-Wiedemann syndrome (BWS).
• Spectrin depleted melanoma cells cell cycle arrest in the G1 phase.
• aII-spectrin binds to DNA at the sites of damage and acts as a scaffold, recruiting of repair proteins.
• Decreased cell growth and survival.
Spectrin contributes with actin to cell adhesionand spreading
• Spectrin depleted cells exhibited modifications of the actincytoskeleton,such as loss of stress fibers, alterations of focal contacts and modified expression of some integrins.
Control of activation of transmembrane proteins
• Spectrin-based skeleton via its two major proteins, spectrin and ankyrin, directly binds CD45 in lymphocytes.
• Spectrin aggregates contain several proteins, such as hsp70, receptor for activated C kinase-1 (RAC-1) and PKCh.
• Participation of spectrin in signaling function in lymphocytes.
• PKCh relationship to spectrin and its participation in regulating early steps of apoptosis.
Spectrin functions can be regulated by posttranslationalmodifications
Spectrin posttranslational regulation-apoptosis/necrosis,secretion/endocytosis, vertebrate lens development,pathologies in the central nervous system.
• b-Spectrin phosphorylationessential in destabilization of the erythrocyte membrane skeleton.
• Proteolysis of spectrin .
Spectrin Plays a Critical Role in Platelet Formation
• Diane Krause, MD, PhD http://www.hematology.org/Publications/Hematologist/2011/6988.aspx September 1, 2011
• Using a novel spectrintetramer-disrupting protein
• During megakaryocytematuration, an extensive invaginated membrane system forms. Without intact spectrintetramers, megakaryocyteslacked this extensive membrane structure.
Shigella flexneri utilize the spectrin cytoskeleton during invasion and comet tail generation
• http://www.ncbi.nlm.nih.gov/pubmed/22424399
• Tyson J Ruetz1, Ann E Lin1 and Julian A Guttman* 2012 Mar 16
• Following internalization, all three proteins are recruited to the internalized bacteria, spectrinrecruitment to those structures in the absence of adducin or p4.1.
• Invasion of intestinal epithelial cells and comet tail-based motility in host cells are key for S. flexneri to access replicativeniches and disseminate throughout host tissues [2].
BIBLIOGRAPHY
• www.ncbi.nlm.nih.gov/pubmed/22424399
• www.hematology.org/Publications/Hematologist/2011/6988.
• Spectrin-based skeleton as an actor in cell signaling B. Machnicka • R. Grochowalska • D. M. Bogusławska •A. F. Sikorski • M. C. Lecomte Published: 30 August 2011 Springerlink.com
• en.wikipedia.org/wiki/Spectrin