The Golgi in Cell Migration: Regulation by Signal Transduction and Its Implications for Cancer Cell Metastasis

Migration and invasion are fundamental features of metastatic cancer cells. The Golgi apparatus, an organelle involved in posttranslational modification and sorting of proteins, is widely accepted to regulate directional cell migration. In addition, mounting evidence suggests that the Golgi is a hub for different signaling pathways. In this paper we will give an overview on how polarized secretion and microtubule nucleation at the Golgi regulate directional cell migration. We will review different signaling pathways that signal to and from the Golgi. Finally, we will discuss how these signaling pathways regulate the role of the Golgi in cell migration and invasion. We propose that by identifying regulators of the Golgi, we might be able to uncover unappreciated modulators of cell migration. Uncovering the regulatory network that orchestrates cell migration is of fundamental importance for the development of new therapeutic strategies against cancer cell metastasis

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A minimum-labeling approach for reconstructing protein networks acros

Adaptation of endoplasmic reticulum exit sites to acute and chronic increases in cargo load

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102229/1/emboj2008136.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102229/2/emboj2008136-sup-0001.pd

Bio-Zombie: the rise of pseudoenzymes in biology

Pseudoenzymes are catalytically dead counterparts of enzymes. Despite their first description some 50 years ago, the importance and functional diversity of these ‘fit-for-purpose’ polypeptides is only now being appreciated. Pseudoenzymes have been identified throughout all the kingdoms of life and, owing to predicted deficits in enzyme activity due to the absence of catalytic residues, have been variously referred to as pseudoenzymes, non-enzymes, dead enzymes, prozymes or ‘zombie’ proteins. An important goal of the recent Biochemical Society Pseudoenzymes-focused meeting was to explore the functional and evolutionary diversity of pseudoenzymes and to begin to evaluate their functions in biology, including cell signalling and metabolism. Here, we summarise the impressive breadth of enzyme classes that are known to have pseudoenzyme counterparts and present examples of known cellular functions. We predict that the next decades will represent golden years for the analysis of pseudoenzymes.</jats:p

RNA, a new member in the glycan-club that gets exposed at the cell surface

In this article we discuss implications of the recent discovery of glycoRNAs found to be present at the cell surface of mammalian cells which was reported by Flynn et al. Cell 2021

MAPK signaling to the early secretory pathway revealed by kinase/phosphatase functional screening

An RNAi screen determines that the early secretory pathway is subject to phosphoregulation via a variety of signaling pathways, including a link between growth factor signaling and ER export

Mechanical strain stimulates COPII‐dependent secretory trafficking via Rac1

Cells are constantly exposed to various chemical and physical stimuli. While much has been learned about the biochemical factors that regulate secretory trafficking from the endoplasmic reticulum (ER), much less is known about whether and how this trafficking is subject to regulation by mechanical signals. Here, we show that subjecting cells to mechanical strain both induces the formation of ER exit sites (ERES) and accelerates ER‐to‐Golgi trafficking. We found that cells with impaired ERES function were less capable of expanding their surface area when placed under mechanical stress and were more prone to develop plasma membrane defects when subjected to stretching. Thus, coupling of ERES function to mechanotransduction appears to confer resistance of cells to mechanical stress. Furthermore, we show that the coupling of mechanotransduction to ERES formation was mediated via a previously unappreciated ER‐localized pool of the small GTPase Rac1. Mechanistically, we show that Rac1 interacts with the small GTPase Sar1 to drive budding of COPII carriers and stimulates ER‐to‐Golgi transport. This interaction therefore represents an unprecedented link between mechanical strain and export from the ER