Related Experiment Video
Updated: Jun 11, 2026
07:26
Single-molecule Super-resolution Imaging of Phosphatidylinositol 4,5-bisphosphate in the Plasma Membrane with Novel Fluorescent Probes
Published on: October 15, 2016
Phospholipids regulate localization and activity of mDia1 formin
Nagendran Ramalingam1, Hongxia Zhao, Dennis Breitsprecher
1Institute for Anatomy and Cell Biology, Ludwig-Maximilians-Universitaet, Muenchen, Schillerstr. 42, 80336 Muenchen, Germany.
European Journal of Cell Biology
|July 13, 2010
Summary
Mouse formin mDia1 localization and activity are regulated by phospholipids. Positively charged regions bind to the plasma membrane, anchoring mDia1, while C-terminal interactions transiently inactivate its actin assembly function.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Diaphanous-related formins (DRFs) are key regulators of actin cytoskeleton dynamics.
- GTPase regulation of formin activity and localization is well-studied.
- Other regulatory mechanisms for formin subcellular distribution and activity remain unclear.
Purpose of the Study:
- To investigate the role of phospholipids in regulating mouse formin mDia1 activity and localization.
- To identify the specific regions of mDia1 involved in phospholipid interactions.
- To elucidate the functional consequences of these interactions on mDia1 behavior.
Main Methods:
- Reconstitution of plasma membrane bilayers.
- Biochemical assays to study mDia1 binding to phospholipids.
- Analysis of mDia1's effect on actin filament assembly in the presence of phospholipids.
- Identification of phospholipid-binding sites within mDia1.
Main Results:
- mDia1 possesses phospholipid-binding sites in its N-terminal basic domain (BD) and C-terminal region.
- The N-terminal BD binds to phosphatidylinositol-4,5-bisphosphate (PIP(2)), clustering it and anchoring mDia1 to the membrane.
- Phospholipid interaction with the C-terminus significantly reduces mDia1's actin filament assembly activity.
Conclusions:
- Phospholipids play a dual role in regulating mDia1.
- N-terminal phospholipid binding anchors mDia1 to the plasma membrane.
- C-terminal phospholipid interaction acts as a switch for transient mDia1 inactivation.
Related Concept Videos
01:42Phosphoinositides and PIPs
Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
01:39Mechanism of Filopodia Formation
Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
01:11IP3/DAG Signaling Pathway
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...
01:31Mechanism of Lamellipodia Formation
Cells migrating in response to external stimuli form lamellipodia, which are thin membrane protrusions supported by a mesh of linked, branched, or unbranched actin filaments. These actin filaments interact with myosin motor proteins, creating the dynamic actomyosin complex within the cytoskeleton. Contractility, or the ability to generate contractile stress, is inherent to the actomyosin complex. It helps cells detect the stiffness of the surrounding ECM and exert contractile force for...
01:19Fluid Mosaic Model
Scientists identified the plasma membrane in the 1890s and its principal chemical components (lipids and proteins) by 1915. The model for plasma membrane structure, proposed in 1935 by Hugh Davson and James Danielli, was the first model to be widely accepted in the scientific community. The model was based on the plasma membrane's "railroad track" appearance in early electron micrographs. Davson and Danielli theorized that the plasma membrane's structure resembled a sandwich with the analogy of...
01:34Fluid Mosaic Model
The fluid mosaic model was first proposed as a visual representation of research observations. The model comprises the composition and dynamics of membranes and serves as a foundation for future membrane-related studies. The model depicts the structure of the plasma membrane with a variety of components, which include phospholipids, proteins, and carbohydrates. These integral molecules are loosely bound, defining the cell’s border and providing fluidity for optimal function.LipidsThe most...