Field Lab Projects

NIH3T3 fibroblast produces PtdIns(3,4,5)P3 in response to PDGF.

Didn't you always want to move to Southern California to make movies?

Overview

Our lab studies the phosphoinositides, a group of signaling molecules involved in growth factor signaling, membrane trafficking, and probably many more functions. We are taking several approaches to identify novel functions for this interesting group of signaling molecules. One approach uses fluorescence microscopy of living mammalian cells expressing green fluorescent protein reporters for each of the phosphoinositides. Another approach involves a screen of the entire Drosophila proteome to identify novel phosphoinositide-binding proteins. Both approaches have yielded new and unexpected functions for the phosphoinositides. For example, we have identified an interesting role for PI(4,5)P2 at the cleavage furrow during mitotic cytokinesis. We have many projects to study our new phosphoinositide binding proteins (including their role in cytokinesis) and to develop new approaches to study phosphoinositide function. Because of the broad role for phosphoinositides in the cell, we are always ready to delve into new areas of cell biology as our research leads us.

General strategies to study phosphoinositides

• Live cell imaging of phosphoinositides

Changes in the level or sub-cellular localization of a phosphoinositide can provide a clue to new functions.

Proof of principle:

A role for PtdIns(4,5)P2 at the cleavage furrow during cytokinesis

We have found that PtdIns(4,5)P2 specifically accumulates at the cleavage furrow during cytokinesis. We have also shown that two of the PI(4)P-5-kinases that generate PtdIns(4,5)P2 also localize to the cleavage furrow. Furthermore, interference with PtdIns(4,5)P2 interferes with cytokinesis. Finally, we have evidence that PtdIns(4,5)P2 may be the key to answering an important unsolved issue in cytokinesis: what causes the plasma membrane to adhere to the contractile ring so that it invaginates during cytokinesis?

Investigation of this role for PtdIns(4,5)P2 at the cleavage furrow is the basis of several projects in the Field laboratory. As a good start, we have identified a novel PtdIns(4,5)P2 binding protein (see below) that functions during cytokinesis.

PtdIns(4,5)P2 accumulates at the cleavage furrow during cytokinesis.

		• Discover new phosphoinositide binding proteins We have devised a high-throughput screen to identify new phosphoinositide-binding proteins. After screening approximately 1/3 of the Drosophila proteome we have already identified many new phosphoinositide-binding proteins. Each of these provides the basis for new projects to study questions of structure-function, and to study the function of each protein as a mediator of the effects of phosphoinositides within the cell.

You can also find research summaries for our lab at the following sites:

Seth Field's Lab

Studying Phosphoinositides at UCSD