All cells have surface membranes and maintaining the surface area of this membrane is critical to the normal functioning of cells. The surface membranes of cells lining our lungs, guts and the light-sensing cells of our eyes undergo constant recycling to operate effectively. Using the light-sensitive membranes in fruit fly eyes as a model system, scientists from the National Centre for Biological Sciences (NCBS), Bangalore, and the Babraham Institute, Cambridge, UK have recently found a critical link – an enzyme named Phospholipase D or PLD – that is essential for proper recycling of membranes to sustain normal sight.

Keywords: eyes, light-sensing membrane, Phospholipase D (PLD), membrane turnover, maintaining membrane size

Every cell has a membrane that defines its boundaries. Maintaining the surface area of this membrane is critical for a range of normal cell functions. For example, the expanded surface membranes of the cells lining our lungs are crucial for absorbing oxygen. Similar surfaces in the cells lining our guts are essential to take in nutrients. In the eyes, the extended surfaces of light-sensitive membranes help us see.  

To function normally, all these membranes undergo a constant process of recycling. Scientists from the National Centre for Biological Sciences (NCBS), Bangalore, and the Babraham Institute in UK have recently found a critical player essential for proper membrane recycling.

Using the light-sensitive membranes of fruit-fly eyes as a model system, the researchers have discovered that the enzyme Phospholipase D or PLD is necessary for membrane recycling to sustain normal sight. Their results could help in understanding membrane turnover, a process that occurs in almost every cell in our bodies.

Within our eyes, are millions of photoreceptors – nerve cells that capture light to form images of the world around us. The surface membranes of these nerve cells are packed with rhodopsin, a protein that detects light. These are the light-sensing membranes of the eyes that absorb packets of light to trigger nerves causing the sensation of sight.   

Once triggered by light, however, rhodopsin molecules must be ‘reset’ in order to sense light again. This begins with a process called endocytosis, where the cell pinches off parts of its surface membranes into structures called endosomes. The rhodopsin in endosomes is eventually recycled back onto the cell surface for further events of light detection. Since a photoreceptor’s sensitivity depends on how many rhodopsin molecules it has on its surface, membrane turnover in these cells is critical in preserving normal eyesight.

“You can think of endocytosis and membrane recycling as two arms of the membrane turnover process,” says Raghu Padinjat from NCBS. “There needs to be a balance between the two, or else the size of the membrane will shrink – a condition that could lead to retinal degeneration in the eyes. This is actually seen in an inherited genetic disease, a rare disorder called Best’s macular degeneration,” he adds.

However, the connection between endocytosis and the eventual recycling process to maintain surface membranes have remained unclear – until now. A collaborative study from Padinjat’s laboratory at NCBS and the Babraham Institute in UK, has found that a well-known enzyme called Phospholipase D or PLD plays a central role in linking endocytosis to membrane recycling.

Using fruit fly eyes as a model system, the team has found that when these cells are exposed to light, PLD is switched on, and that its activity is essential in coupling endocytosis with recycling of rhodopsin back to the cell surface.

In mutant flies that lack PLD in their photoreceptors, the endocytosis process is unlinked from membrane recycling. When exposed continuously to light, the cell surface of photoreceptors in mutant flies gradually shrinks, with reducing rhodopsin levels that make it progressively less sensitive to light. Without PLD activity, the retina gradually degenerates and mutant flies go blind.

But the results from this study are not limited only to membrane turnover in the light-sensitive membranes of the eyes. Every cell in our body undergoes membrane turnover for a variety of reasons – from resetting detectors on their surfaces to changing the molecules on their membranes in response to a signal.

“During membrane turnover, some surface membrane comes into the cell via endocytosis, and this incoming membrane also needs to be recycled back because every cell needs to maintain a balance. Otherwise, the system will collapse,” says Rajan Thakur, a researcher from Padijat’s group and the primary author of a publication in the journal eLife that reports these results.

“Therefore regardless of what the cell type it is, there need to be mechanisms to couple endocytosis with recycling of membrane,” says Padinjat. “And that is the importance of our work – we define a mechanism by which cell membrane size is regulated,” he adds.

About the paper:

The research described here has been published as a paper titled "PhospholipaseD activity couples plasma membrane endocytosis with retromer dependent recycling" in the journal eLife in Novmber 2016. The paper can be accessed at https://elifesciences.org/content/5/e18515

About the authors:

Rajan Thakur is affiliated to the National Centre for Biological Sciences (NCBS), Bangalore,

Aniruddha Panda is affiliated to the National Centre for Biological Sciences (NCBS), Bangalore

Elise Coessens, Qifeng Zhang, Plamen Georgiev, Michael J.O. Wakelam, and Nicholas Ktistakis are or were previously affiliated to the Inositide Laboratory, Babraham Institute, Cambridge, UK

Nikita Raj, Shweta Yadav, Sruthi Balakrishnan, Bishal Basak and Renu Pasricha are affiliated to the National Centre for Biological Sciences (NCBS), Bangalore, India

Prof Raghu Padinjat is affiliated to the National Centre for Biological Sciences (NCBS), Bangalore

Contact:

Prof Raghu Padinjat is open to being contacted by e-mail at praghu@ncbs.res.in

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