Information about Gelsolin

gelsolin (amyloidosis, Finnish type)
Identifiers
Symbol	GSN
Entrez	2934
HUGO	4620
OMIM	137350
RefSeq	NM_198252
UniProt	P06396
Other data
Locus	Chr. 9 q33

Gelsolin is an actin-binding protein that is a key regulator of actin filament assembly and disassembly. Gelsolin is one of the most potent members of the actin-severing gelsolin/villin superfamily, as it severs with nearly 100% efficiency.^[1] Gelsolin is located intracellularly (in cytosol and mitochondria) and extracellularly (in blood plasma).^[2]

Structure

Gelsolin is an 82-kD protein with six homologous subdomains, referred to as S1-S6. Each subdomain is composed of a five-stranded β-sheet, flanked by two α-helices, one positioned perpendicular with respect to the strands and one positioned parallel. The N-terminal (S1-S3) forms an extended β-sheet, as does the C-terminal (S4-S6).^[3]

Regulation

Among the lipid binding actin regulatory proteins, gelsolin (along with cofilin) is one of the few that exhibit preferential binding towards polyphosphoinositide (PPIs).^[4] The binding sequences in gelsolin closely resemble the motifs in the other PPI-binding proteins.<ref name="Yu" />

Gelsolin's activity is stimulated by calcium ions (Ca2+).<ref name="Sun" /> Although the protein retains its overall structural integrity in both activated and deactivated states, the S6 helical tail moves like a latch depending on the concentration of calcium ions.^[5] The C-terminal end detects the calcium concentration within the cell. When there is no Ca2+ present, the tail of S6 shields the actin-binding sites on one of S2's helices.<ref name="Kiselar" /> When a calcium ion attaches to the S6 tail, however, it straightens, exposing the S2 actin-binding sites.<ref name="Burtnik" /> The N-terminal is directly involved in the severing of actin. S2 and S3 bind to the actin before the binding of S1 severs actin-actin bonds and caps the barbed end.<ref name="Yu" />

Gelsolin can be inhibited by a local rise in the concentration of phosphatidylinositol (4,5)-bisphosphate (PIP₂), a PPI. This is a two step process. Firstly, (PIP₂) binds to S2 and S3, inhibiting gelsolin from actin side binding. Then, (PIP₂) binds to gelsolin’s S1, preventing gelsolin from severing actin, although (PIP₂) does not bind directly to gelsolin's actin-binding site.<ref name="Yu" />

Gelsolin's severing of actin, in contrast to the severing of microtubules by katanin, does not require any extra energy input.

Cellular Function

As an important actin regulator, gelsolin plays a role in podosome formation (along with Arp3, cortactin, and Rho GTPases).^[6]

Gelsolin also inhibits apoptosis by stabilizing the mitochondria <ref name="Koya" />. Prior to cell death, mitochondria normally lose membrane potential and become more permeable. Gelsolin can impede the release of cytochrome C, obstructing the signal amplification that would have led to apoptosis.

Organismal Relevance

Research in mice suggests that gelsolin, like other actin-severing proteins, is not expressed to a significant degree until after the early embryonic stage--approximately 2 weeks in murine embryos.^[7] In adult specimens, however, gelsolin is particularly important in motile cells, such as blood platelets. Mice with null gelsolin-coding genes undergo normal embryonic development, but the deformation of their blood platelets reduced their motility, resulting in a slower response to wound healing.<ref name="Witke" />

An insufficiency of gelsolin in mice has also been shown to cause increased permeability of the vascular pulmonary barrier, suggesting that gelsolin is important in the response to lung injury.^[8]

References

See Also

• Cortactin
• Villin

External links

• MeSH Gelsolin

•  • [ e] Cell signaling: calcium signaling
Second messengers	IP3 - NAADP - cADPR
Intracellular calcium store gates	IP3 receptor - Ryanodine receptor - putative NAADP receptor
Calcium pumps and exchangers	SERCA - Na/Ca antiport - Ca/H antiport
calcium binding protein domains	EF hand domain - C2 domain
Calcium based molecular switches, and kinases	Troponin C - CaM - CaM kinases - PKC - NCS
Intracellular calcium chelators (calcium buffers) and calcium sensors	Calbindin - S100 - pervalbumin - Calretinin - Calsequestrin - Sarcalumenin - Phospholamban - Synaptotagmins
Calcium dependent proteases	Calpain
Calcium dependent cytoskeleton remodeling proteins	Gelsolin
Cell membrane calcium channels	VDCC - TRP - NMDA receptor - AMPA receptor - 5-HT3 receptor - P2X Receptor
Calcium regulated chaperones	calreticulin - calnexin
Calcium based adhesion molecules	Cadherin
Calcium homeostasis	Parathyroid hormone - Calcitonin - calcium receptor - vitamin D

•  • [ e] Carrier protein: calcium-binding proteins
Intracellular calcium-sensing proteins	Calmodulin - Calnexin - Calreticulin - Gelsolin - neuronal (Hippocalcin, Neurocalcin, Recoverin)
Other	Annexin (A1, A2, A5) - Vitamin D-dependent calcium-binding protein/Calbindin - Calexcitin - Calsequestrin - Osteocalcin - Osteonectin - S-100 - Synaptotagmin - Troponin C

•  • [ e] Proteins of the cytoskeleton
Microfilaments	Actins - Actin-binding proteins - Actinin - Arp2/3 complex - Cofilin - Destrin - Gelsolin - Myosins - Profilin - Tropomodulin - Troponin (T, C, I) - Tropomyosin - Wiskott-Aldrich syndrome protein
Intermediate filaments	type 1 and 2 (Cytokeratin, type I, type II) - type 3 (Desmin, GFAP, Peripherin, Vimentin) - type 4 (Internexin, Nestin, Neurofilament, Synemin, Syncoilin) - type 5 (Lamin A, B)
Microtubules	Dyneins - Kinesins - MAPs (Tau protein, Dynamin) - Tubulins - Stathmin
Catenins	Alpha catenin - Beta catenin - Plakoglobin (gamma catenin) - Delta catenin
Nonhuman	Major sperm proteins - Prokaryotic cytoskeleton (Crescentin, FtsZ, MreB)
Other	APC - Dystrophin (Dystroglycan) - plakin (Desmoplakin, Plectin) - Spectrin - Talin - Utrophin - Vinculin