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