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ANTONIO RODRÍGUEZ ARTALEJO AN. R. ACAD. NAC. FARM.

genetics and molecular biology has led to a remarkable advancement in our un-
derstanding of molecular mechanisms of exocytosis. Here, I review recent studies
on a simple cellular model widely used in neurosecretion research, the adrenal
chromaffin cell, and discuss the specific roles in different steps of the exocytotic
process that has been assigned to several synaptic proteins.

Key words: Exocytosis.—Chromaffin cell.—SNARE.—Synaptotagmin.—Neuro-
secretion.

EXTENSIVE ABSTRACT

Molecular determinants of exocytosis in adrenomedullary chromaffin cells

Cell to cell communication provides the basis of functional integration in
multicellular organisms. This process makes use of extracellular messengers
—neurotransmitters and hormones— that are released by the cells in response to
a wide range of stimuli. A paradigmatic example of intercellular communication
is that occurs at the synapses between two neurons. The preynaptic side of this
structure is contributed by the nerve ending where the transmitter is stored is
discrete amounts —known as quanta— inside membrane vesicles. Communication
is mediated by the release of the trasmitter into the synaptic cleft and the subse-
quent activation of specific receptors located on the plasma membrane of the
postsynaptic cell. The mechanism by which transmitters are released is the exo-
cytosis, which implies the fusion of the plasma membrane with the vesicle mem-
brane and the establishment of a diffusional pathway between the vesicle interior
ant the extracellular space. Only a fraction of the vesicles that are in physical
contact —docked— with the plasma membrane are competent —primed— for being
exocytosed, a phenomenon that is triggered or accelerated by a rise in the intra-
cellular free Ca2+ concentration. The purpose of this review is to describe the
molecular machinery, mostly composed of proteins, involved in the last steps of
the exocytotic process: vesicle docking, vesicle priming and fusion of the vesicle
membrane with the plasma membrane. On each of these steps, a set of three
proteins play a central role: Synaptobrevin, a vesicle-associated membrane protein
—also known as VAMP—, and two plasma membrane proteins, syntaxin and
SNAP25 (synaptosome-associated protein of 25 kDa). These three proteins form
the so-called fusion complex, which binds to two soluble proteins, NSF (N-ethyl-
maleimide-sensitive fusion protein) and a-SNAP (soluble NSF attachment protein).
Since a-SNAP directly interacts with synaptobrevin, syntaxin and SNAP25, these
proteins are commonly referred to as SNAP receptors or SNARES. NSF, a-SNAP
and SNARES constitute a molecular apparatus that has been conserved through
the evolutionary scale and is essential to any process of membrane fusion. NSF
acts as an ATPase whose activity is stimulated by a-SNAP leading to fusion com-
plex disassembly. Moreover, continuous formation and disruption of the fusion
complex is an intrinsic feature to the SNARE functioning in membrane trafficking.

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