Membrane Fusion and Exocytosis
Examples of Exocytosis
An example of regulated exocytosis is the secretion of neurotransmitters in neurons [6]. SNARES aid in the docking and fusion of synaptic vesicles containing neurotransmitters to the nerves terminal membrane. Fusion of the two membranes allows exocytosis of neurotransmitters across synaptic cleft. This process is stimulated by Ca2+ influx.
Another example of regulated exocytosis is in the pancreas. Exocytosis of insulin and glucagon from the islets of Langerhan is stimulated by a change in blood glucose concentration [3]. When blood glucose concentration is high, insulin is secreted from beta cells. Whereas, when blood glucose concentration is low glucagon is secreted from alpha cells.
What is Exocytosis?
Exocytosis is the process of exporting materials from inside the cell through the fusion of vesicles to the plasma membrane [1]. Exocytosis is performed for a variety of reasons from removal of waste products to chemical signalling [2]. There are two main types of exocytosis: regulated and constitutive. Regulated exocytosis is where exocytosis is caused as a result of a stimulus such as a hormone or neurotransmitter [3]. Whereas, constitutive exocytosis is where materials are exported from the cell regularly. Exocytosis can be characterised into stages: docking, fusion and secretion.
Role of Rabs in Exocytosis
Rabs are proteins which are capable of recognising target sites. Each type of Rab is responsible for mediating a different step within the processes involved inside the cell. For example, Rab 11 and 7 are responsible for mediating endocytosis, Rab 2 is responsible for mediating intra-golgi transport and Rab 8, 10 and 3 are responsible for mediating the docking process within exocytosis. When a vesicle is in close proximity to the target membrane, Rab docks to the tethering protein located on the target membrane and the vesicle [4]. There are 2 types of tethering protein: highly elongated fibrous protein and multiprotein complexes [4]. This tethering allows the vesicle to be in close enough proximity for fusion to occur.
Role of SNAREs in Exocytosis
Fusion occur between the vesicle membrane and the target plasma membrane in order to allow exocytosis to occur. SNARES (Soluble NSF-sensitive factor Attachment REceptors ) play a vital role in the fusion to these 2 membranes. There are 36 different SNARES in each human cell, however SNARES can be classified into two main categories: V-SNARES and T-SNARES [5]. T-SNARES are comprised of 2 or 3 proteins and are located in the target membrane, whereas V-SNARES are a single chain found in the vesicle membrane. However, both of these SNARES have helical domains which interact and wrap around each other forming a stable 4 helix bundle consisting of 3 T-SNARES and 1 V-SNARE, locking the membranes together [2]. Further twisting of the SNARES pulls the membranes together. This forces water to be expelled from between the two membranes and a connecting stalk to form. Hemifusion occurs in which partial fusion forms a new bilayer [6]. Complete fusion causes this new bilayer to rupture, creating a pore, allowing materials to exit the vesicle and leave the cell. Once secretion is undergone NSF and SNAP facilitate the dissociation of SNARES from the empty vesicle [6].
Figure 1. The interaction and twisting of SNAREs to give rise to membrane fusion (7)
