Study uncovers key mechanisms of cell communication

Feb 07, 2011 By Krishna Ramanujan
Top panel: a fluorescence microscopy image of dividing cells showing the plasma membrane (PM, red) and endoplasmic reticulum (ER, green), with a boxed region showing a PM-ER membrane contact site. Bottom panel: High-resolution electron microscopy of a region of a cell where the ER (green) is near the PM (red). Image: Emr Lab

(PhysOrg.com) -- A unique bridging process may be behind a mystery of intracellular communication, according to new Cornell research published Feb. 4 in the journal Cell.

Researchers at Cornell's Weill Institute for Cell and Molecular Biology have uncovered how certain signaling molecules in the cell are regulated.

The signaling molecules, called phosphoinositide (PI) lipids, are key components of the plasma membrane that surrounds a cell. PI lipids are important in signaling processes involved in cell growth and development, responses to extracellular signals, and transport pathways in and out of the cell. Misregulation of PI lipids has been linked to several diseases, including cancer, diabetes, and developmental and .

"All inherited disorders correspond to defects at the ," said Scott Emr, director of the Weill Institute and senior author of the paper. "Understanding the fundamental aspects of the cellular basis of these signaling pathways is absolutely essential to understand and treat diseases like cancer."

Much like an on-and-off switch, many cellular actions, including the functions of PI lipids, are activated by attaching a phosphate group to proteins or lipids (a process called phosphorylation), and similarly, deactivated by the removal of the phosphate group. A class of enzymes called phosphatases mediates the removal of .

"Previous research has focused on the enzymes called kinases that add phosphates to proteins or lipids (on-switch). We considered the alternative that phosphatases (off-switch) have crucial roles in regulating essential signaling pathways that take place at the ," explained first-author Chris Stefan, a senior research associate in Emr's lab.

The researchers studied a PI phosphatase called sac1, an enzyme that resides in the endoplasmic reticulum, an organelle inside the cell responsible for the synthesis of proteins and lipids and for regulating calcium signaling.

"The puzzle was how sac1 in the endoplasmic reticulum regulates PI lipids in a distinct membrane compartment, the plasma membrane," said Stefan.

"We discovered that a family of proteins, called osh proteins, provides the molecular bridge between PI lipids in the plasma membrane and the phosphatase sac1 in the endoplasmic reticulum," explained co-author and graduate student Andrew Manford.

The osh proteins sense PI lipid levels and respond by creating a kind of scaffolding between the and endoplasmic reticulum, providing the missing link between these two distinct membrane systems. This allows the sac1 phosphatase to shut down PI lipids during communication between these two separate cellular compartments.

Explore further: Molecular gate that could keep cancer cells locked up

Related Stories

Cornell researchers reveal structure of key protein

Apr 21, 2010

(PhysOrg.com) -- For the first time, researchers -- all Cornell scientists -- have characterized the structure of a protein that belongs to certain enzymes that are essential for proper functioning in all ...

Chemists get grip on slippery lipids

Aug 30, 2007

The ability of the body's cells to correctly receive and convey signals is crucial to good health. Lipids, or fats, play a critical role in this regulation by providing spaces for proteins to gather and network. They are ...

Researchers ID molecular link key for cell growth

Jan 24, 2011

(PhysOrg.com) -- When a cell is preparing to grow or replicate, it starts the way a monarch planning to expand his territory might: by identifying and marshaling the necessary resources, loading them onto ...

Recommended for you

Molecular gate that could keep cancer cells locked up

2 hours ago

In a study published today in Genes & Development, Dr Christian Speck from the MRC Clinical Sciences Centre's DNA Replication group, in collaboration with Brookhaven National Laboratory (BNL), New York, ...

The 'memory' of starvation is in your genes

5 hours ago

During the winter of 1944, the Nazis blocked food supplies to the western Netherlands, creating a period of widespread famine and devastation. The impact of starvation on expectant mothers produced one of the first known ...

Sugar mimics guide stem cells toward neural fate

Jul 30, 2014

Embryonic stem cells can develop into a multitude of cells types. Researchers would like to understand how to channel that development into the specific types of mature cells that make up the organs and other structures of ...

User comments : 0