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Shreya Ray

20091069

Membrane Phosphatidylserine Regulates Surface Charge and

Protein LocalizationYeung et al. 2008 Science

Abstract:

There are likely to be many factors that direct and regulate the targeting to proteins to specific sub-

cellular membrane domains. One of the major factors could be something as simple as electric

charge! In this paper, the author describes the observed localisation and protein-directing activity of

membrane phosphatidylserine, a moderately negatively charged phospholipid. For this purpose, he

has developed a new probe lact-C2 (from lactadherin, a milk glycoprotein) which selectively binds

only phophatidylserine. Further, he has co-expressed this protein with GFP or RFP to directly observe

the co-localisation of lact-C2 and phosphatidylserine. Tt the amount of phosphatidylserine in a

membrane plays a major role in deciding its charge. More phosphatidylserine can be added to a

membrane to make it more negatively charged and vice-versa. This phenomenon is directly used for

targetting cationic proteins to the required membrane by controlling its charge. It was observed that

cationic proteins that are normally present in the plasma membrane are relocalized to endocytic

compartments (which are less negative due to less amount of phosphatidylserine) when the plasma

membrane surface charge falls as a result of calcium influx.

Techniques used:

1. Liposomes of different lipid compositions: to test probe2. Fluorescent-tagging: genetically encoded fluorescent biosensor3. Confocal microscopy: to view cell layers and cell internal4. Fluorescent cationic surface charge probes: to characterise localisation of charges inside cell5. Recombinant DNA technology: to genetically modify/ control protein expression.

Major take-home:

Electric charge can play a major role in protein-targeting. Since the membrane charge is a function of

phosphatidylserine content, controlling this could be an important step in some signal transductionprocesses, where by altering the membrane charges we could induce cationic proteins to move from

one membrane to another within the cell. Another way we could use electric charge to direct a

protein is via post-translational modifications in order to alter the charge on the expressed protein

so that it matches the charge on the membrane where we want to express it.

Suggest one experiment that would advance concepts described in the paper:

We could perhaps extend similar treatment to neurons, both during the development of the growth

cone in response to extracellular signals, as well as during signalling processes via synapse, in order

to see how much of a role electric charge really plays in the life of cells during crucial processes.