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. 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. 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. 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. 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. 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. 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. 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. 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. 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].
