SNARE

SNARE Proteins

SNARE proteins are a large protein superfamily consisting of more than 60 members in yeast and mammalian cells. They are essential for the process of vesicle fusion, which is a critical step in the transport of molecules within cells. SNAREs are involved in the fusion of vesicles with target membranes, a process that is fundamental to neurotransmitter release, hormone secretion, and membrane trafficking.

Structure and Function

SNARE proteins are characterized by the presence of a SNARE motif, which is a stretch of 60-70 amino acids that forms a coiled-coil structure. SNAREs are classified into two main types based on their location and function:

• v-SNAREs (vesicle SNAREs): These are located on the vesicle membrane. An example is synaptobrevin, which is found on synaptic vesicles.
• t-SNAREs (target SNAREs): These are located on the target membrane. Examples include syntaxin and SNAP-25, which are found on the plasma membrane.

The interaction between v-SNAREs and t-SNAREs forms a SNARE complex, which brings the vesicle and target membranes into close proximity, facilitating membrane fusion.

Mechanism of Action

The SNARE complex formation is a highly regulated process that involves several steps:

1. Docking: The vesicle approaches the target membrane, guided by Rab GTPases and tethering factors. 2. Priming: The SNARE proteins on the vesicle and target membranes partially assemble into a trans-SNARE complex. 3. Fusion: The trans-SNARE complex zippers up, pulling the membranes together and facilitating the fusion of the lipid bilayers. 4. Disassembly: After fusion, the SNARE complex is disassembled by the ATPase NSF and its cofactor α-SNAP, allowing the SNAREs to be recycled.

Biological Importance

SNARE proteins are crucial for various cellular processes, including:

• Neurotransmitter Release: In neurons, SNAREs mediate the release of neurotransmitters at synapses, which is essential for neuronal communication.
• Hormone Secretion: SNAREs are involved in the secretion of hormones from endocrine cells.
• Membrane Trafficking: SNAREs facilitate the transport of proteins and lipids between different cellular compartments.

Clinical Significance

Dysfunction of SNARE proteins is associated with several diseases, including:

• Botulism and Tetanus: These diseases are caused by bacterial toxins that cleave SNARE proteins, preventing neurotransmitter release and leading to paralysis.
• Neurodegenerative Diseases: Abnormal SNARE function has been implicated in diseases such as Alzheimer's and Parkinson's.

Also see

• Vesicle trafficking
• Neurotransmitter release
• Membrane fusion
• Rab GTPases