Table 4.

Examples of PS-binding proteins

Proteins	Function
Rho GTPases	A family of 20 proteins in mammals controlling endocytosis, cell migration, cell progression and morphology92,93. Cdc4261 is discussed in the main text. It has been proposed that the size of the positive charge in the C-terminal area of Rho1 and Cdc42 is important for the specificity of binding to PS94. It is not known how many of the Rho GTPases that bind PS.
Rab GTPases and Rab11-FIPsa	Distinct associations between the PS-probe LactC2, Rab GTPases and Rab11-FIPs, suggesting that C2 domains are not the sole mechanism for Rab11-FIPs to associate with PS-containing membranes95.
K-Ras	K-Ras (see48 for a review) is a GTPase and an early player in many signal transduction pathways. The protein is prenylated and bound to membranes96. The KRAS-BRAF-MEK pathway requires the presence of both PS and the lysine-rich C-terminus of KRAS97. PS is important for binding and nanoclustering of K-Ras at the plasma membrane98. The highest colocalization between K-Ras and PS observed in BHK cells is with PS species containing C18:1 in the sn-2 position48.
Protein kinase C	Enzyme family controlling the function of other proteins through phosphorylations99.
Akt (Protein kinase B)	Activation of Akt mediates downstream responses through protein phosphorylations; Akt activation relies on binding to both PI(3,4,5)P3 and PS100.
EHD1	Transport through recycling endosomes81 and further to the Golgi apparatus101.
Evectin-2	Retrograde transport through endosomes to the Golgi apparatus80.
ATP9A	Flippase colocalizing with PS in endosomes82.
Synaptotagmin	Ca2+-triggered PS binding has multiple functions in exocytosis, including stabilisation of open fusion pores by retarding the rate of fusion pore dilation102.
Cavins	Cavins contain PS-binding domains; cavins are able to associate into oligomers and are present in caveolae103 which are enriched in PS in the inner leaflet58. Cavin-1 forms polyhedral lattices on PS-containing liposomes104. PS is required for cavin-1 and caveolin-1 to form stable caveolae in vivo60.
Caveolins	Caveolins are together with cavins important for formation of caveolae and can as cavins form oligomers103. Since caveolins also bind to cholesterol105, one may speculate if caveolins together with cavins induce clusters of PS. Knock-down of caveolin-1 resulted in reorganisation of PS within the plasma membrane106.
Myosin-1A	Myosin-1A binds to liposomes composed of PS and PI (4,5)P2 and colocalized with PS-binding and PI(4,5)P2-binding probes. Only the PS-binding probe (Lact-C2) reduced brush border targeting of a C-terminal domain of myosin-1A107. Myosin-1A is a candidate for linking actin and PS.
Spectrin	PS-binding sites identified108; spectrin plays an important role in maintenance of plasma membrane integrity and cytoskeletal structure109. Spectrin is a candidate for linking actin and PS.
Proteins transporting PS from ER to the plasma membrane	Oxysterol-binding proteins in Saccharomyces cerevisae bind PS and contribute to PS transport to the plasma membrane110. In HeLa cells the human homologues ORP5 and ORP8 mediate ER-plasma membrane contact and deliver PS from the ER to the plasma membrane111.

^aFIPs: family interacting proteins.