Endocytosis and Exocytosis

Endocytosis and exocytosis are the membrane-trafficking processes that move bulk cargo into and out of cells using lipid vesicles. In endocytosis, the plasma membrane invaginates and pinches off to internalize material; in exocytosis, intracellular vesicles fuse with the plasma membrane to release their contents. Together they allow cells to take up nutrients and receptors, secrete proteins and neurotransmitters, and continually remodel their surface.

Definition

Endocytosis is the uptake of extracellular material into the cell within membrane-bounded vesicles formed by inward budding of the plasma membrane; exocytosis is the release of intracellular material to the exterior by fusion of secretory vesicles with the plasma membrane.

Scope

The entry covers the major endocytic routes (clathrin-mediated and clathrin-independent pathways), the regulated and constitutive modes of exocytosis, and the membrane-fusion machinery — especially SNARE proteins — that drives vesicle fusion. It treats vesicular trafficking as a reference topic in cell biology and is not clinical guidance.

Core questions

• How does the plasma membrane bend and bud to internalize cargo?
• Which pathways internalize cargo with and without clathrin?
• How do vesicles fuse with target membranes to release their contents?
• What distinguishes constitutive from regulated secretion?

Key concepts

• Clathrin-mediated endocytosis
• Clathrin-independent endocytosis
• Phagocytosis and pinocytosis
• Coated pits and vesicle budding
• Constitutive versus regulated exocytosis
• SNARE-mediated membrane fusion
• Vesicle recycling at the plasma membrane

Key theories

SNARE hypothesis of membrane fusion

Vesicle and target-membrane SNARE proteins zipper into a tight complex that pulls the two bilayers together and catalyzes fusion, providing a common molecular basis for exocytosis and other fusion events.

Mechanisms

In endocytosis, cytosolic coat proteins and membrane-bending proteins deform a patch of plasma membrane into an invagination that buds inward as a vesicle. The best-characterized route is clathrin-mediated endocytosis, in which clathrin assembles a lattice at coated pits to internalize receptors and their ligands; several clathrin-independent pathways also operate, varying in their cargo and machinery. The internalized vesicle sheds its coat and is sorted through the endosomal system. Exocytosis runs in the opposite direction: secretory vesicles are delivered to the plasma membrane, where SNARE proteins on the vesicle and target membrane assemble into a four-helix complex that forces the bilayers together and drives fusion, releasing cargo. Secretion is constitutive when vesicles fuse continuously, or regulated when fusion awaits a trigger such as a rise in intracellular calcium, as at the nerve terminal. Imaging methods that visualize events within tens of nanometres of the plasma membrane have allowed these budding and fusion steps to be observed in real time.

Clinical relevance

Endocytosis and exocytosis underlie processes such as receptor regulation, antigen uptake, neurotransmitter and hormone release, and the entry routes exploited by some pathogens and toxins, so they are foundational for understanding cell physiology. This entry describes trafficking mechanisms for reference and is not a basis for diagnosis or treatment.

History

Vesicular uptake and secretion were recognized morphologically by electron microscopy in the mid-twentieth century, and clathrin-coated pits were identified as a defined endocytic structure. The molecular machinery was then resolved: clathrin and adaptor proteins for coat assembly, and the SNARE proteins whose discovery clarified how vesicle fusion is achieved. Live-cell imaging later allowed single budding and fusion events to be watched directly, and additional clathrin-independent routes were progressively mapped.

Key figures

• Thomas C. Südhof
• James E. Rothman
• Harvey T. McMahon
• Satyajit Mayor

Seminal works

• sudhof-rothman-2009
• doherty-mcmahon-2009

Frequently asked questions

What is the difference between endocytosis and exocytosis?

Endocytosis brings material into the cell by budding vesicles inward from the plasma membrane, while exocytosis releases material from the cell by fusing intracellular vesicles with the plasma membrane.

What are SNARE proteins?

SNARE proteins are membrane proteins on a vesicle and its target membrane that assemble into a tight complex, pulling the two bilayers together to drive fusion during exocytosis and related events.