A model for the self-organization of vesicular flux and protein distributions in the Golgi apparatus

TL;DR

This paper presents a model explaining how the Golgi apparatus maintains its complex protein and vesicle distributions through SNARE gradients and vesicle flux, even with minimal SNARE pairs.

Contribution

The model demonstrates how Golgi cisternae's composition can be maintained with only one or two SNARE pairs, highlighting the role of SNARE decay and vesicle flux in self-organization.

Findings

SNARE gradients drive retrograde vesicle flux.

Steady-state SNARE concentration decays exponentially with cisterna number.

Vesicle populations differ in cargo and recycling behavior.

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 the 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 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.