Abstract
The generation of two non-identical membrane compartments via exchange of vesicles is considered to require two types of vesicles specified by distinct cytosolic coats that selectively recruit cargo, and two membrane-bound SNARE pairs that specify fusion and differ in their affinities for each type of vesicles. The mammalian Golgi complex is composed of 6–8 non-identical cisternae that undergo gradual maturation and replacement yet features only two SNARE pairs. We present a model that explains how distinct composition of Golgi cisternae can be generated with two and even a single SNARE pair and one vesicle coat. A decay of active SNARE concentration in aging cisternae provides the seed for a cis trans SNARE gradient that generates the predominantly retrograde vesicle flux which further enhances the gradient. This flux in turn yields the observed inhomogeneous steady-state distribution of Golgi enzymes, which compete with each other and with the SNAREs for incorporation into transport vesicles. We show analytically that the steady state SNARE concentration decays exponentially with the cisterna number. Numerical solutions of rate equations reproduce the experimentally observed SNARE gradients, overlapping enzyme peaks in cis, medial and trans and the reported change in vesicle nature across the Golgi: Vesicles originating from younger cisternae mostly contain Golgi enzymes and SNAREs enriched in these cisternae and extensively recycle through the Endoplasmic Reticulum (ER), while the other subpopulation of vesicles contains Golgi proteins prevalent in older cisternae and hardly reaches the ER.
Highlights
The Golgi apparatus is composed of multiple compartments, called cisternae, typically 6–8 in mammalian cells
We have developed a quantitative model to address a fundamental question in cell biology: How does the Golgi apparatus, an organelle composed of multiple cisternae that exchange vesicles, steadily maintains its inhomogeneous protein composition in the face of ongoing cisternal aging and replacement, and cargo entry and exit
Competition of enzymes for incorporation into predominantly retrograde-fusing vesicles in turn generates overlapping but distinct stationary enzyme peaks. Applying these general mechanisms of fusion asymmetry and competitive vesicle loading to the actual situation in the stacked mammalian Golgi, we reproduced the experimentally observed distributions of the two sensitive factor Attachment protein Receptors (SNAREs) pairs that operate in the Golgi, and enzyme peaks in cis, medial and trans cisternae
Summary
The Golgi apparatus is composed of multiple compartments, called cisternae, typically 6–8 in mammalian cells. The individual cisternae are enriched in glycosylation and other enzymes, which form distinct but overlapping gradients with peaks in the cis, medial or trans cisternae [1]. As anterograde cargo traverses the Golgi apparatus from cis to trans, it becomes modified by Golgi enzymes in an assembly-line fashion. The cisternal maturation hypothesis is best supported by all available experimental data [3], [4]. According to this concept, cargo enters the Golgi by fusion of Endoplasmic Reticulum (ER)-derived vesicles with each other that form a new cisterna at the cis face of the Golgi. Individual cisternae mature by shedding their characteristic Golgi enzymes and at the same time acquiring Golgi resident proteins from the more trans cisterna [5], [6] (Fig. 1A)
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