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2006 ; 10
(2
): 423-7
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Membrane fusion in cells: molecular machinery and mechanisms
#MMPMID16796809
Leabu M
J Cell Mol Med
2006[Apr]; 10
(2
): 423-7
PMID16796809
show ga
Membrane fusion is a sine qua non process for cell physiology. It is critical for
membrane biogenesis, intracellular traffic, and cell secretion. Although
investigated for over a century, only in the last 15 years, the molecular
machinery and mechanism of membrane fusion has been deciphered. The membrane
fusion event elicits essentially three actors on stage: anionic phospholipids -
phosphatidylinositols, phosphatidyl serines, specific membrane proteins, and the
calcium ions, all participating in a well orchestrated symphony. Three soluble
N-ethylmaleimide-sensitive factor (NSF)-attachment protein receptors (SNAREs)
have been implicated in membrane fusion. Target membrane proteins, SNAP-25 and
syntaxin (t- SNARE) and secretory vesicle-associated membrane protein (v-SNARE)
or VAMPwere discovered in the 1990's and suggested to be the minimal fusion
machinery. Subsequently, the molecular mechanism of SNARE-induced membrane fusion
was discovered. It was demonstrated that when t-SNARE-associated lipid membrane
is exposed to v-SNARE-associated vesicles in the presence of Ca(2+), the SNARE
proteins interact in a circular array to form conducting channels, thus
establishing continuity between the opposing bilayers. Further it was proved that
SNAREs bring opposing bilayers close to within a distance of 2-3 Angstroms,
allowing Ca(2+) to bridge them. The bridging of bilayers by Ca(2+) then leads to
the expulsion of water between the bilayers at the contact site, allowing lipid
mixing and membrane fusion. Calcium bridging of opposing bilayers leads to the
release of water, both from the water shell of hydrated Ca(2+) ions, as well as
the displacement of loosely coordinated water at the phosphate head groups in the
lipid membrane. These discoveries provided for the first time, the molecular
mechanism of SNARE-induced membrane fusion in cells. Some of the seminal
discoveries are briefly discussed in this minireview.
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