Flotillin: Difference between revisions

← Older edit Newer edit →

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Orly Spivak, Michal Harel, Joel L. Sussman

@@ Line 5: / Line 5: @@
 Flotillins are highly conserved among species. For example, mouse and human flotillin-1 share a 98.1% identical amino acid sequence. Even between vertebrates and invertebrates the similarity is more than 60%, implicating that flotillins are important for cell physiology.
-Officially, flotillins belong to the group of SPFH domain containing proteins. <scene name='60/607923/Mouse_flotillin_2/3'>TextToBeDisplayed</scene>
+Officially, flotillins belong to the group of SPFH domain containing proteins. <scene name='60/607923/Mouse_flotillin_2/3'>Spfh Domain Of Mouse Stomatin (Crystal Form 1)</scene>
 <StructureSection load='3rec' size='350' side='right' caption='Escherichia coli reca protein-bound DNA (PDB entry [[3rec]])' scene=''></StructureSection>
-This SPFH (stomatin/prohibitin/flotillin/HflK/C) domain and a C-terminal “flotillin domain” comprising alanine and glutamic acid repeats are the only recognizable domains within the flotillin protein. The SPFH domain, also referred to as prohibitin homology (PHB) domain, was first identified in stomatin and is shared by several pro- and eukaryotic proteins. However, the function of the SPFH domain is still unknown. Most SPFH domain containing proteins tend to form oligomers, as was shown for stomatin, podocin, prohibitin and flotillins, although the SPFH domain does not mediate the oligomerization of flotillins. Another common feature of SPFH proteins is their association with lipid rafts. Typical with the SPFH domain containing proteins, flotillins also tend to form hetero- as well as homo-oligomers, but this oligomerization requires the flotillin domain [20,21] and tyrosine residue 163 of flotillin-2. Flotillins stabilize each other, which became obvious upon siRNA mediated knockdown of either flotillin-1 or -2 and concomitant decrease in the expression of the other one. Notably, this interdependency is stronger in the case of flotillin-1, since flotillin-1 depletion typically results in only a moderate or even no depletion of flotillin-2, suggesting that flotillin-1 is more dependent on flotillin-2 than vice versa. Flotillins were originally believed to be transmembrane proteins that are enriched in caveolae which are a subtype of membrane rafts. However, this has been disputed in later studies where it was clearly shown that flotillins reside within non-caveolar rafts. In general, membrane rafts are defined as dynamic, nanoscale membrane microdomains enriched in cholesterol and glycosphingolipids, which function as sorting platforms for various cellular processes. Meanwhile, flotillins are
+This SPFH (stomatin/prohibitin/flotillin/HflK/C) domain and a C-terminal “flotillin domain” comprising alanine and glutamic acid repeats are the only recognizable domains within the flotillin protein. The SPFH domain, also referred to as prohibitin homology (PHB) domain, was first identified in stomatin and is shared by several pro- and eukaryotic proteins. However, the function of the SPFH domain is still unknown. Most SPFH domain containing proteins tend to form oligomers, as was shown for stomatin, podocin, prohibitin and flotillins, although the SPFH domain does not mediate the oligomerization of flotillins. Another common feature of SPFH proteins is their association with lipid rafts. Typical with the SPFH domain containing proteins, flotillins also tend to form hetero- as well as homo-oligomers, but this oligomerization requires the flotillin domain and tyrosine residue 163 of flotillin-2. Flotillins stabilize each other, which became obvious upon siRNA mediated knockdown of either flotillin-1 or -2 and concomitant decrease in the expression of the other one. Notably, this interdependency is stronger in the case of flotillin-1, since flotillin-1 depletion typically results in only a moderate or even no depletion of flotillin-2, suggesting that flotillin-1 is more dependent on flotillin-2 than vice versa. Flotillins were originally believed to be transmembrane proteins that are enriched in caveolae which are a subtype of membrane rafts. However, this has been disputed in later studies where it was clearly shown that flotillins reside within non-caveolar rafts. In general, membrane rafts are defined as dynamic, nanoscale membrane microdomains enriched in cholesterol and glycosphingolipids, which function as sorting platforms for various cellular processes. Meanwhile, flotillins are
 widely used as membrane raft marker proteins. In contrast to what was assumed originally, they do not traverse the membrane, but are attached to the cytosolic leaflet of the plasma membrane by means of fatty acid modifications and possibly hydrophobic stretches in the case of flotillin-1. Furthermore, flotillins harbor several putative, conserved phosphorylation sites , for some of which (i.e., Tyr160 for flotillin-1, Tyr163 for flotillin-2) a functional role has been shown. Flotillins are expressed ubiquitously, and their expression is particularly high in brain, heart, lung, and placenta, but fairly low in pancreas and liver. Despite their ubiquitous tissue distribution, the expression of flotillins underlies, at least to some extent, transcriptional regulation and can be fine-tuned by different transcription factors.
-<scene name='60/607923/Mouse_flotillin_2/1'>TextToBeDisplayed</scene>
+<scene name='60/607923/Mouse_flotillin_2/1'>7 Domain Of The Mouse Flotillin 2</scene>
-<scene name='60/607923/Mouse_flotillin_2/2'>TextToBeDisplayed</scene>
+<scene name='60/607923/Mouse_flotillin_2/2'>7 Domain Of The Mouse Flotillin 2 with colors</scene>
 == Function ==
@@ Line 22: / Line 22: @@
-</StructureSection>
 == References ==
 .	Banning A, Kurrle N, Meister M and Tikkanen R, Flotillins in Receptor Tyrosine Kinase Signaling and Cancer. Cells. 2014 Feb 19;3(1):129-49.