Intermediate compartment (IC): from pre-Golgi vacuoles to a semi-autonomous membrane system

Abstract

Despite its discovery more than three decades ago and well-established role in protein sorting and trafficking in the early secretory pathway, the intermediate compartment (IC) has remained enigmatic. The prevailing view is that the IC evolved as a specialized organelle to mediate long-distance endoplasmic reticulum (ER)–Golgi communication in metazoan cells, but is lacking in other eukaryotes, such as plants and fungi. However, this distinction is difficult to reconcile with the high conservation of the core machineries that regulate early secretory trafficking from yeast to man. Also, it has remained unclear whether the pleiomorphic IC components—vacuoles, tubules and vesicles—represent transient transport carriers or building blocks of a permanent pre-Golgi organelle. Interestingly, recent studies have revealed that the IC maintains its compositional, structural and spatial properties throughout the cell cycle, supporting a model that combines the dynamic and stable aspects of the organelle. Moreover, the IC has been assigned novel functions, such as cell signaling, Golgi-independent trafficking and autophagy. The emerging permanent nature of the IC and its connections with the centrosome and the endocytic recycling system encourage reconsideration of its relationship with the Golgi ribbon, role in Golgi biogenesis and ubiquitous presence in eukaryotic cells.

An international cohort study of autosomal dominant tubulointerstitial kidney disease due to mutations identifies distinct clinical subtypes

“…Such an effect is suggested by specific accumulation of proteins with prosegment mutations (vs. other REN mutations) in the ER-Golgi intermediate compartment, where the quality control system of the early secretory pathway and the concentration process of nascent secretory proteins into secretory granules take place. 31 The age of presentation and severity of prosegment mutations may vary significantly due to the type of mutation and its specific effects on biosynthesis, cellular trafficking, and proteolytic processing of prorenin and renin activity regulation. In addition to causing cellular toxicity, these dominant negative effects may be due to abnormal interactions between the mutant and wild-type proteins that are being processed in parallel, as seen in early-onset insulin-deficient diabetes.…”

Editorial: Golgi Dynamics in Physiological and Pathological Conditions

“…In the course of these events, repositioning of Golgi elements is typically observed in the perinuclear region of many vertebrate cells, controlled by the duplicated centrosome and centrosome-nucleated microtubules of the forming mitotic spindle (Mascanzoni et al). Notably, the pulling apart of the centrosomes during the late G2/early mitosis is accompanied by the evidently equal partitioning of the intermediate compartment (IC), a permanent membrane network that-unlike the Golgi stacks-keeps its properties during mitosis (Saraste and Marie, 2018).…”

“…In a new view of the Golgi ribbon, the non-compact zones linking the cisternal stacks are jointly occupied by the permanent IC elements and recycling endosomes (RE). As mentioned above, as a prelude for cell division, the stacks that undergo reversible break-down disconnect from these centrosome-linked compartments, which as a consequence would be allowed move to the spindle poles for partitioning into the forming daughter cells (Saraste and Marie, 2018;Saraste and Prydz).…”

Organelle Inheritance Control of Mitotic Entry and Progression: Implications for Tissue Homeostasis and Disease

“…An additional contribution to the inhibition of the membrane fusion machineries is provided by the HACE1-mediated monoubiquitination of the SNARE protein syntaxin 5 (Huang et al, 2016). As a result, the Golgi membranes are consumed by an extensive vesiculation during metaphase, when they become dispersed into vesicular/tubular clusters, with some intermediate compartment (IC) and Golgi proteins redistributed into the Endoplasmic Reticulum (ER) (Figure 2D; Saraste and Marie, 2018). Then, during telophase and cytokinesis, the dispersed Golgi proteins and membranes are gradually reassembled into a GC in each of the daughter cells (Figure 2E; Shorter and Warren, 2002; Altan-Bonnet et al, 2004; Colanzi and Corda, 2007).…”