The Physiological Functions of the Golgin Vesicle Tethering Proteins

Abstract

The golgins comprise a family of vesicle tethering proteins that act in a selective manner to tether transport vesicles at the Golgi apparatus. Tethering is followed by membrane fusion to complete the delivery of vesicle-bound cargo to the Golgi. Different golgins are localized to different regions of the Golgi, and their ability to selectively tether transport vesicles is important for the specificity of vesicle traffic in the secretory pathway. In recent years, our mechanistic understanding of golgin-mediated tethering has greatly improved. We are also beginning to appreciate how the loss of golgin function can impact upon physiological processes through the use of animal models and the study of human disease. These approaches have revealed that loss of a golgin causes tissue-restricted phenotypes, which can vary in severity and the cell types affected. In many cases, it is possible to attribute these phenotypes to a defect in vesicular traffic, although why certain tissues are sensitive to loss of a particular golgin is still, in most cases, unclear. Here, I will summarize recent progress in our understanding of golgins, focusing on the physiological roles of these proteins, as determined from animal models and the study of disease in humans. I will describe what these in vivo analyses have taught us, as well as highlight less understood aspects, and areas for future investigations.

Golgi outposts locally regulate microtubule orientation in neurons but are not required for the overall polarity of the dendritic cytoskeleton

“…To determine whether Golgi outposts function to create or maintain the dendrite-specific orientation of microtubules, we analyzed microtubule polarity in neurons in which we eliminated the cis-Golgi matrix protein GM130. GM130 has the potential to both recruit the protein machinery for MTOC activities (microtubule nucleation, anchoring, and stabilization) and contribute to forming multi-compartment Golgi units (Barr et al, 1997;Kondylis et al, 2005;Liu et al, 2017;Lowe, 2019;Martin and Akhmanova, 2018;Nakamura et al, 1995;Sanders and Kaverina, 2015;Zhou et al, 2014). We found that the percentage of multi-compartment outposts decreases when GM130 is absent, which supports the model that GM130 participates in connecting Golgi compartments in neurons ( Figure 1D) (Zhou et al, 2014).…”

“…We targeted the cis-Golgi matrix protein GM130, which has two key roles: first, work done in mammalian cells has shown that GM130 recruits AKAP450, which in turn recruits protein complexes that nucleate, tether, and stabilize microtubules (Hurtado et al, 2011;Rivero et al, 2009;Roubin et al, 2013;Wu and Akhmanova, 2017). Second, GM130 is needed for proper Golgi structure and connects Golgi compartments to form multi-compartment units, including outposts (Barr et al, 1997;Kondylis et al, 2005;Liu et al, 2017;Lowe, 2019;Nakamura et al, 1995;Zhou et al, 2014). Strikingly, we found that the global orientation of dendritic microtubules is unaffected by the loss of GM130 or the fly AKAP450 ortholog plp.…”

Maintaining order: COG complex controls Golgi trafficking, processing, and sorting

“…Coiled‐coil tethers, as their name suggests, consist of a long coiled‐coil structure often terminating with a noncoiled‐coil head domain, and, many if not all CCTs function as dimers . Most of the known CCTs reside at the Golgi and are often called Golgins . Although CCTs all have a similar structure, they vary greatly in size (from ~ 50 to ~ 400 kDa).…”

Rapid degradation of GRASP55 and GRASP65 reveals their immediate impact on the Golgi structure

“…Most vertebrate cells contain 100-200 stacks, each comprised of four to six cisternae (Storrie et al, 2012;Sin and Harrison, 2016). In addition, these stacked cisternae are laterally interconnected into a single, contiguous ribbon-like entity that is positioned next to the centrosomes in the perinuclear region (Lowe, 2019). By joining adjacent cisternae between stacks, the Golgi can accommodate and process large secretory cargos that do not fit into individual cisternae such as collagen or Weibel-Palade bodies (Ferraro et al, 2014;Lavieu et al, 2014).…”