4.4 Article

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

Journal

HISTOCHEMISTRY AND CELL BIOLOGY
Volume 158, Issue 3, Pages 229-240

Publisher

SPRINGER
DOI: 10.1007/s00418-022-02121-0

Keywords

Golgi complex; Blood-urine barrier; Urothelium; Differentiation; Bladder cancer; Uroplakins

Funding

  1. Slovenian Research Agency (ARRS) [J7-2594, P3-0108]
  2. INTAS [99-4-1732]
  3. Telethon [E.1105]
  4. Consorzio Mario Negri, Italy
  5. Italian National Research Council (Convenzione CNR-CMN Sud)
  6. MRIC UL [IP-0510]

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The Golgi complex undergoes structural remodeling during the differentiation of urothelial cells, which contributes to the formation of the blood-urine barrier. Uroplakins (UPs), the most abundant membrane proteins in differentiated urothelial cells, play a crucial role in the barrier's formation by their structural organization and hindering endocytosis. Golgi fragmentation is necessary for the delivery of specific differentiation cargos to the plasma membrane and cell-cell communication. Understanding the contribution of the Golgi complex to the blood-urine barrier is important for both normal urothelial cells and cancer cells.
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.

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