Spectrins its
structure,function
and role in animal
cells
INTRODUcTION
• Spectrin is a cytoskeletal protein.
• First isolated as a major protein
component of human red blood
cells....
Spectrins: several genes and numerous isoforms widely
distributed in all metazoan cells
• Exist mainly as heterotetramers
...
Spectrins are a structural platform for stabilization
and activation of membrane microdomains
• Spectrin-based skeleton
pa...
Spectrins are multifunctional proteins involved
in regulation of cell morphology and mechanical
properties
• Hereditary he...
Spectrins, cell cycle and DNA repair
• The presence of spectrin in a
complex including TGFb-R1-
Beckwith-Wiedemann syndrom...
Spectrin contributes with actin to cell adhesion
and spreading
• Spectrin depleted cells exhibited modifications of the ac...
Control of activation of transmembrane proteins
• Spectrin-based skeleton via its two
major proteins, spectrin and
ankyrin...
Spectrin functions can be regulated by posttranslational
modifications
Spectrin posttranslational
regulation-
apoptosis/ne...
Spectrin Plays a Critical Role in Platelet Formation
• Diane Krause, MD, PhD
http://www.hematology.org/P
ublications/Hemat...
Shigella flexneri utilize the spectrin cytoskeleton
during invasion and comet tail generation
• http://www.ncbi.nlm.nih.go...
BIBLIOGRAPHY
• www.ncbi.nlm.nih.gov/pubmed/22424399
• www.hematology.org/Publications/Hematologist/2011/6988.
• Spectrin-b...
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Spectrins its structure,function and role in animal cells

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Spectrins its structure,function and role in animal cells

  1. 1. Spectrins its structure,function and role in animal cells
  2. 2. 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.
  3. 3. Spectrins: several genes and numerous isoforms widely distributed in all metazoan cells • Exist mainly as heterotetramers made 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 spectrin repeats, 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.
  4. 4. Spectrins are a structural platform for stabilization and 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.
  5. 5. Spectrins are multifunctional proteins involved in 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 squamous morphology. • a- and b-spectrins are required during nervous system development-NCAM.
  6. 6. 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.
  7. 7. Spectrin contributes with actin to cell adhesion and spreading • Spectrin depleted cells exhibited modifications of the actin cytoskeleton,such as loss of stress fibers, alterations of focal contacts and modified expression of some integrins.
  8. 8. 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.
  9. 9. Spectrin functions can be regulated by posttranslational modifications Spectrin posttranslational regulation- apoptosis/necrosis,secretion/ endocytosis, vertebrate lens development,pathologies in the central nervous system. • b-Spectrin phosphorylation essential in destabilization of the erythrocyte membrane skeleton. • Proteolysis of spectrin .
  10. 10. Spectrin Plays a Critical Role in Platelet Formation • Diane Krause, MD, PhD http://www.hematology.org/P ublications/Hematologist/201 1/6988.aspx September 1, 2011 • Using a novel spectrin tetramer-disrupting protein • During megakaryocyte maturation, an extensive invaginated membrane system forms. Without intact spectrin tetramers, megakaryocytes lacked this extensive membrane structure.
  11. 11. Shigella flexneri utilize the spectrin cytoskeleton during invasion and comet tail generation • http://www.ncbi.nlm.nih.gov/pub med/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, spectrin recruitment 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 replicative niches and disseminate throughout host tissues [2].
  12. 12. 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

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