Disease relevance of Flot1

• Ischemia did not affect the yield, density, flotillin-1 or cholesterol content of lipid rafts [1].

High impact information on Flot1

• These results suggest that flotillin-1 is an essential molecule in IgE receptor-mediated mast cell activation, and regulates the kinase activity of Lyn in lipid rafts [2].
• In the flotillin-1 KD cells, we observed a significant decrease in Ca(2+) mobilization, the phosphorylation of ERKs, tyrosine phosphorylation of the gamma-subunit of IgE receptor, and IgE receptor-mediated degranulation [2].
• In this study we have used discontinuous sucrose density gradients, Western blot analysis, and cholesterol measurements to show that recombinant and smooth muscle (rat tail artery, vas deferens, and bladder) P2X1 receptors are present in cholesterol-rich lipid rafts and co-localize with the lipid raft markers flotillin-1 and -2 [3].
• The sucrose density gradient fractionation of the cell lysate revealed that TrkA primarily located in the lipid raft fraction moved to the non-raft fraction in GM1+ cells. p75NTR and Ras also moved from the raft to non-raft fraction in GM1+ cells, whereas flotillin and GM1 persistently resided in the lipid raft [4].
• We find that immunopurified adipocyte caveolae have a relatively limited protein composition, and they lack the raft protein, flotillin, and insulin receptors [5].

Biological context of Flot1

• Identification of reggie-1 and reggie-2 as plasmamembrane-associated proteins which cocluster with activated GPI-anchored cell adhesion molecules in non-caveolar micropatches in neurons [6].
• Sertoli cells and Sertoli DIG fractions were found to lack the common raft-associated protein, caveolin, a marker protein for caveolae, but they are enriched in the 48-kd protein, flotillin-1, a protein also implicated in raft formation, cell signaling, and cell motility [7].
• It is significant that there is an increased gene expression of flotillin-1 in the Parkinson substantia nigra/ventral tegmental area [8].
• However, the total cellular levels of caveolin and flotillin, proteins implicated in insulin signal transduction/compartmentalization, were markedly elevated in skeletal muscles from SHRSP compared with WKY animals [9].

Anatomical context of Flot1

• Flotillin-1 and BCtheta were mostly colocalized in double immunolabeling on a part of the plasma membranes of small processes and secondary lysosome membranes [10].
• Ultrastructural localization of flotillin-1 to cholesterol-rich membrane microdomains, rafts, in rat brain tissue [10].
• In addition, the membrane of lysosome and Golgi apparatus were frequently labeled for flotillin-1 with a patchy pattern [10].
• Flotillin-1- and BCtheta-labeled areas were patchy and prominent on the plasma membranes of small processes and synapses in the neuropil [10].
• Here we show that the preformed reggie/flotillin caps present in resting T cells act as priming platforms for macrodomain assembly [11].

Associations of Flot1 with chemical compounds

• The nitrated proteins were localized to the raft fraction obtained by centrifugation of the homogenate in a sucrose density gradient, which contained specific raft markers such as flotillin-1 and caveolin-1 [12].
• After disruption of the microdomains by cholesterol extraction with cyclodextrin, a subcomplex of several GIC proteins including the B-subunit of the vacuolar ATPase, flotillin-1, caveolin, and p17 could still be isolated by immunoprecipitation [13].
• In the rat brain, the most prominent observation was the revelation of all catecholamine cells (dopamine, norepinephrine, epinephrine) by the flotillin-1 antibody (1:100 dilution) [8].

Physical interactions of Flot1

• Thus, the preformed reggie/flotillin caps are stable priming platforms for the assembly of multiprotein complexes controlling actin reorganization during T cell activation [11].

Other interactions of Flot1

• Thus, reggie-1 and reggie-2 identify sites where activated GPI-linked CAMs preferentially accumulate and which may represent noncaveolar micropatches (domains) [6].
• Both alpha- and beta-tubulin were detected in the rat brain raft fraction as abundant proteins, which co-immunoprecipitate with flotillin-1 and caveolin-1 [12].
• Characterization of membrane rafts isolated from rat sertoli cell cultures: caveolin and flotillin-1 content [7].

Analytical, diagnostic and therapeutic context of Flot1

• We examined the ultrastructure of rafts in rat brain tissue by pre-embedding immunoelectron microscopy using flotillin-1 antibody, which is a biochemical marker of lipid rafts, and BCtheta, which is nicked and biotinylated theta-toxin, and binds to membrane cholesterol of rafts [10].

References