Vesicle transport

Introduction

Vesicle transport is a fundamental cellular process that involves the movement of materials within membrane-bound sacs called vesicles. This mechanism is crucial for maintaining cellular homeostasis, facilitating communication between different cellular compartments, and ensuring the proper functioning of cells. Vesicle transport is involved in numerous cellular activities, including the secretion of proteins, the uptake of nutrients, and the recycling of cellular components.

Vesicle Formation

Vesicle formation is the initial step in vesicle transport. It involves the budding of vesicles from donor membranes, such as the endoplasmic reticulum (ER), the Golgi apparatus, or the plasma membrane. This process is highly regulated and involves several key proteins, including coat proteins like clathrin, COPI, and COPII.

Clathrin-Coated Vesicles

Clathrin-coated vesicles are involved in endocytosis and the transport of materials from the Golgi apparatus to lysosomes. The formation of these vesicles begins with the recruitment of clathrin triskelions to the membrane, where they assemble into a basket-like structure. This assembly is facilitated by adaptor proteins, such as AP2, which link clathrin to the membrane and select cargo molecules for transport.

COPI and COPII-Coated Vesicles

COPI-coated vesicles mediate retrograde transport from the Golgi to the ER, while COPII-coated vesicles are responsible for anterograde transport from the ER to the Golgi. The assembly of COPI and COPII vesicles involves the recruitment of coat protein complexes to the membrane, where they induce curvature and budding. The selection of cargo is mediated by specific cargo receptors that interact with the coat proteins.

Vesicle Targeting and Fusion

Once formed, vesicles must be accurately targeted to their destination membranes. This process involves several key steps, including vesicle tethering, docking, and fusion.

Tethering

Vesicle tethering is the initial contact between a vesicle and its target membrane. This step is mediated by tethering factors, such as Rab GTPases and tethering complexes like the exocyst complex. These proteins ensure that vesicles are directed to the correct membrane compartment.

Docking

Following tethering, vesicles undergo docking, a process that brings the vesicle and target membranes into close proximity. This step is mediated by SNARE proteins, which form a complex that bridges the two membranes. The SNARE complex is composed of v-SNAREs on the vesicle and t-SNAREs on the target membrane.

Fusion

The final step in vesicle transport is membrane fusion, where the lipid bilayers of the vesicle and target membrane merge. This process is driven by the SNARE complex, which facilitates the mixing of lipid bilayers and the release of vesicle contents into the target compartment. Fusion is regulated by additional proteins, such as NSF and SNAPs, which disassemble the SNARE complex after fusion.

Regulation of Vesicle Transport

Vesicle transport is tightly regulated to ensure specificity and efficiency. This regulation involves various signaling pathways and molecular switches, such as GTPases, kinases, and phosphatases.

Role of GTPases

GTPases, such as Rab and Arf proteins, act as molecular switches that regulate vesicle transport by cycling between active GTP-bound and inactive GDP-bound states. These proteins control various aspects of vesicle transport, including vesicle budding, motility, and fusion.

Phosphoinositides

Phosphoinositides are a class of phospholipids that play a crucial role in vesicle transport by recruiting specific proteins to membranes. Different phosphoinositide species are distributed in distinct membrane compartments, providing spatial cues for vesicle trafficking.