Membrane Dynamics

What is flotillin-associated endocytosis?

Flotillins, which are proteins that localize to specific microdomains or lipid rafts in the plasma membrane, mediate a clathrin-independent endocytosis pathway that is regulated by the Src family tyrosine kinase Fyn [1], [2]. Flotillins are detergent insoluble and named for the fact that they float in sucrose density gradients (reviewed in [3]). The flotillin family comprises flotillin 1 and flotillin 2 proteins, which are highly homologous (sharing 50% sequence identity).

A clathrin independent pathway mediated by proteins called Flotillins, localized within lipid rafts in plasma membrane. This pathway is regulated by the Src family tyrosine kinase Fyn

They assemble in almost equal amounts at the plasma membrane creating microdomains that bud into the cell [2], [4]. GPI-anchor protein CD59, cholera toxinB subunit (CTxB) are examples of cargo endocytosed via this route [1], [5]. Flotillin-associated endocytosis is either dependent or independent of dynamin depending on the cell type or the cargo endocytosed. Flotillins may also serve as adaptors for other endocytic pathways (reviewed in [3]). Flotillins interact with cortical cytoskeleton and regulates it through association with myosin IIA and this has been shown to control the formation of plasma membrane protrusions at the rear end of motile leukocytes, called uropods [6].

References

1. Glebov OO, Bright NA, and Nichols BJ. Flotillin-1 defines a clathrin-independent endocytic pathway in mammalian cells. Nat. Cell Biol. 2005; 8(1):46-54. [PMID: 16341206]
2. Riento K, Frick M, Schafer I, and Nichols BJ. Endocytosis of flotillin-1 and flotillin-2 is regulated by Fyn kinase. J. Cell. Sci. 2009; 122(Pt 7):912-8. [PMID: 19258392]
3. Otto GP, and Nichols BJ. The roles of flotillin microdomains–endocytosis and beyond. J. Cell. Sci. 2011; 124(Pt 23):3933-40. [PMID: 22194304]
4. Frick M, Bright NA, Riento K, Bray A, Merrified C, and Nichols BJ. Coassembly of flotillins induces formation of membrane microdomains, membrane curvature, and vesicle budding. Curr. Biol. 2007; 17(13):1151-6. [PMID: 17600709]
5. Saslowsky DE, Cho JA, Chinnapen H, Massol RH, Chinnapen DJ, Wagner JS, De Luca HE, Kam W, Paw BH, and Lencer WI. Intoxication of zebrafish and mammalian cells by cholera toxin depends on the flotillin/reggie proteins but not Derlin-1 or -2. J. Clin. Invest. 2010; 120(12):4399-4409. [PMID: 21041954]
6. Meister M, and Tikkanen R. Endocytic trafficking of membrane-bound cargo: a flotillin point of view. Membranes (Basel) 2014; 4(3):356-71. [PMID: 25019426]