The Golgi complex: An organelle that determines urothelial cell biology in health and disease

Abstract

The Golgi complex undergoes considerable structural remodeling during differentiation of urothelial cells in vivo and in vitro. It is known that in a healthy bladder the differentiation from the basal to the superficial cell layer leads to the formation of the tightest barrier in our body, i.e., the blood–urine barrier. In this process, urothelial cells start expressing tight junctional proteins, apical membrane lipids, surface glycans, and integral membrane proteins, the uroplakins (UPs). The latter are the most abundant membrane proteins in the apical plasma membrane of differentiated superficial urothelial cells (UCs) and, in addition to well-developed tight junctions, contribute to the permeability barrier by their structural organization and by hindering endocytosis from the apical plasma membrane. By studying the transport of UPs, we were able to demonstrate their differentiation-dependent effect on the Golgi architecture. Although fragmentation of the Golgi complex is known to be associated with mitosis and apoptosis, we found that the process of Golgi fragmentation is required for delivery of certain specific urothelial differentiation cargoes to the plasma membrane as well as for cell–cell communication. In this review, we will discuss the currently known contribution of the Golgi complex to the formation of the blood–urine barrier in normal UCs and how it may be involved in the loss of the blood–urine barrier in cancer. Some open questions related to the Golgi complex in the urothelium will be highlighted.

Molecular, morphological and functional properties of tunnelling nanotubes between normal and cancer urothelial cells: New insights from the in vitro model mimicking the situation after surgical removal of the urothelial tumor

“…Absence of particular lipid domains in NPU cells could lie in specific protein composition of apical plasma membrane of normal urothelial cells that are in 90% covered by assemblies of uroplakins termed urothelial plaques ( Wu et al, 1990 ; Hu et al, 2000 ). In cancer urothelial cells are uroplakins deficiently expressed ( Kreft et al, 2010b ; Zupančič et al, 2011 ; Višnjar et al, 2017 ; Kreft et al, 2022 ), but enriched in lipid domains ( Resnik et al, 2015 ), giving explanation of OlyA6-negative NPU cells and their TNTs.…”

A Comprehensive Pan-Cancer Analysis of the Tumorigenic Effect of Leucine-Zipper-Like Transcription Regulator (LZTR1) in Human Cancer

“…As a member of the BTB-and kelch-domain-containing (BTB-kelch) superfamily which is generally known to the function through interacting with Cullin3-(CUL3-) based E3 ubiquitin ligases [2,3], LZTR1 is involved in the regulation of cell morphology, gene expression, and other basic cellular processes. Unlike some BTB-kelch proteins that could interact with actin filaments or self-associate into longer homoand heterooligomers [4], LZTR1 was located on the Golgi complex [5], and some studies also reported that the cleav-age of LZTR1 was a necessary condition in the process of Golgi complex disruption which involved in the cell apoptosis [5][6][7][8] suggesting its unique function and status.…”

Biogenesis of specialized lysosomes in differentiated keratinocytes relies on close apposition with the Golgi apparatus

“…But the mechanisms underlying such alteration in Golgi morphology in keratinocytes and, its functional significance remains unclear. Previous studies in other cellular systems show Golgi dispersion in presence of high calcium (Ireland et al, 2020), during mitosis (Colanzi and Corda, 2007), in loss of adhesion (Singh et al, 2018), and also during differentiation (Kreft et al, 2022; Wei and Seemann, 2017) involving different molecular pathways/mechanisms. As keratinocyte differentiation is achieved in presence of high calcium, we hypothesized a possible role of high calcium induced Golgi dispersion through PKC alpha mediated phosphorylation of GRASP55 (Ireland et al, 2020).…”