Related Experiment Video
Updated: Sep 18, 2025

Imaging Local Ca2+ Signals in Cultured Mammalian Cells
Published on: March 3, 2015
PI(4,5)P2 is a master regulator for Ca2+-triggered vesicle exocytosis
Masaki Yamaga1, Thomas F J Martin1
1Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706, USA.
None:
Substantial evidence indicates that phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2] is a plasma membrane phospholipid essential for Ca2+-dependent vesicle exocytosis. Ca2+-triggered vesicle exocytosis is a well-organized multiple-step membrane process including vesicle docking, priming, and soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-dependent fusion. A subset of vesicles are docked on high concentration plasma membrane PI(4,5)P2 microdomains that preferentially undergo exocytosis upon Ca2+-stimulation in neuroendocrine cells. PI(4,5)P2 microdomains also mediate plasma membrane SNARE proteins syntaxin-1 and SNAP-25 partitioning and clustering through electrostatic interactions. PI(4,5)P2 recruits and activates SNARE regulatory proteins such as calcium-dependent activator protein for secretion (CAPS, aka CADPS), mammalian uncoordinated-13 (Munc13), and synaptotagmin-1, which play pivotal roles in the priming and fusion steps of vesicle exocytosis. In this review, we discuss how PI(4,5)P2 controls each step of vesicle exocytosis through PI(4,5)P2-binding effector proteins.
Related Concept Videos
Feedback Regulation of Calcium Concentration
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
Calmodulin-dependent Signaling
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
IP3/DAG Signaling Pathway
Overview of Secretory Vesicles
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...
Fusion of Secretory Vesicles with the Plasma Membrane
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
Pinching-off of Coated Vesicles

