Mitotic cells form actin-based bridges with adjacent cells to provide intercellular communication during rounding

Fykerud, Tone Aase; Knudsen, Lars Mørland; Totland, Max Z.; Sørensen, Vigdis; Dahal‐Koirala, Shiva; Brech, Andreas; Leithe, Edward

doi:10.1080/15384101.2016.1231280

Cited by 17 publications

(15 citation statements)

References 53 publications

(53 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4B), the subtle difference was not significant, consistent with recent work showing cGAS generates only low levels of cGAMP upon activation by chromatin [34,53]. Mitotic cells could potentially take up exogenous cGAMP via the SLC19A1 transporter [76,77] or directly from neighboring cells [78,79]. Recent work has revealed a primordial role for cGAMPdependent STING activation in triggering autophagy through WIPI2/ATG5 in a TBK1/IRF3-independent manner [80].…”

Section: Cgas and Sting Are Non-responsive During Mitosissupporting

confidence: 83%

Attenuation of cGAS/STING Activity During Mitosis

Uhlorn

Gamez

et al. 2019

Preprint

View full text Add to dashboard Cite

The innate immune system recognizes cytosolic DNA associated with microbial infections or cellular stress via the cGAS/STING pathway, leading to activation of phospho-IRF3 and downstream IFN-I and senescence responses. To prevent hyperactivation, cGAS/STING is presumed to be non-responsive to chromosomal self DNA during open mitosis, though specific regulatory mechanisms are lacking. Given a role for the Golgi in STING activation, we investigated the state of the cGAS/STING pathway in interphase cells with artificially vesiculated Golgi and in cells arrested in mitosis. We find that while cGAS activity is impaired through interaction with mitotic chromosomes, Golgi integrity has little effect on the enzyme's production of cGAMP. In contrast, STING activation in response to either foreign DNA (cGAS-dependent) or exogenous cGAMP is impaired by a vesiculated Golgi. Overall our data suggest a secondary means for cells to limit potentially harmful cGAS/STING responses during open mitosis via natural Golgi vesiculation.

show abstract

Section: Cgas and Sting Are Non-responsive During Mitosissupporting

confidence: 83%

Attenuation of cGAS/STING Activity During Mitosis

Uhlorn

Gamez

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…Alternatively, Cx43 might undergo recycling from the multivesicular endosomes to the plasma membrane. In accordance with this model, Cx43 has been shown to be transported to early endosomes during the early phases of mitosis and is thought to undergo recycling to the plasma membrane in the late phases (Boassa et al, 2010;Fykerud et al, 2016;Vanderpuye et al, 2016).…”

Section: Discussionmentioning

confidence: 67%

The E3 ubiquitin ligase NEDD4 induces endocytosis and lysosomal sorting of connexin 43 to promote loss of gap junctions

Totland

Bergsland

Fykerud

et al. 2017

Journal of Cell Science

Self Cite

View full text Add to dashboard Cite

Intercellular communication via gap junctions has an important role in controlling cell growth and in maintaining tissue homeostasis. Connexin 43 (Cx43; also known as GJA1) is the most abundantly expressed gap junction channel protein in humans and acts as a tumor suppressor in multiple tissue types. Cx43 is often dysregulated at the post-translational level during cancer development, resulting in loss of gap junctions. However, the molecular basis underlying the aberrant regulation of Cx43 in cancer cells has remained elusive. Here, we demonstrate that the oncogenic E3 ubiquitin ligase NEDD4 regulates the Cx43 protein level in HeLa cells, both under basal conditions and in response to protein kinase C activation. Furthermore, overexpression of NEDD4, but not a catalytically inactive form of NEDD4, was found to result in nearly complete loss of gap junctions and increased lysosomal degradation of Cx43 in both HeLa and C33A cervical carcinoma cells. Collectively, the data provide new insights into the molecular basis underlying the regulation of gap junction size and represent the first evidence that an oncogenic E3 ubiquitin ligase promotes loss of gap junctions and Cx43 degradation in human carcinoma cells.

show abstract

“…Moreover, connexosomes have been suggested to be able to undergo a transformation into a connexin-enriched multivesicular endosome, which is associated with their fusion with early endosomes [79][80][81][82]. Some studies also indicate that following endocytosis, connexins can under certain conditions undergo recycling from endocytic compartments back to the plasma membrane [32, 75,81,[83][84][85]. It has also been suggested that Cx43 can be transported directly from early secretory compartments to lysosomes without prior transport to the plasma membrane [30].…”

Section: Endocytosis and Degradation Of Gap Junctionsmentioning

confidence: 99%

“…SMURF2 also mediates the PKCinduced endocytosis and degradation of Cx43 [79]. In IAR20 cells, but not in HeLa cells, SMURF2 is also required for the remodeling of Cx43 gap junctions during mitosis [84]. However, it is unclear whether SMURF2 regulates gap junction endocytosis directly by catalyzing Cx43 ubiquitination or indirectly via another, yet unknown, protein [79].…”

Section: Smurf2mentioning

confidence: 99%

Regulation of gap junction intercellular communication by connexin ubiquitination: physiological and pathophysiological implications

Totland

Rasmussen

Knudsen

et al. 2019

Cell. Mol. Life Sci.

Self Cite

111

View full text Add to dashboard Cite

Gap junctions consist of arrays of intercellular channels that enable adjacent cells to communicate both electrically and metabolically. Gap junctions have a wide diversity of physiological functions, playing critical roles in both excitable and non-excitable tissues. Gap junction channels are formed by integral membrane proteins called connexins. Inherited or acquired alterations in connexins are associated with numerous diseases, including heart failure, neuropathologies, deafness, skin disorders, cataracts and cancer. Gap junctions are highly dynamic structures and by modulating the turnover rate of connexins, cells can rapidly alter the number of gap junction channels at the plasma membrane in response to extracellular or intracellular cues. Increasing evidence suggests that ubiquitination has important roles in the regulation of endoplasmic reticulum-associated degradation of connexins as well as in the modulation of gap junction endocytosis and post-endocytic sorting of connexins to lysosomes. In recent years, researchers have also started to provide insights into the physiological roles of connexin ubiquitination in specific tissue types. This review provides an overview of the advances made in understanding the roles of connexin ubiquitination in the regulation of gap junction intercellular communication and discusses the emerging physiological and pathophysiological implications of these processes.

show abstract

Mitotic cells form actin-based bridges with adjacent cells to provide intercellular communication during rounding

Cited by 17 publications

References 53 publications

Attenuation of cGAS/STING Activity During Mitosis

Attenuation of cGAS/STING Activity During Mitosis

The E3 ubiquitin ligase NEDD4 induces endocytosis and lysosomal sorting of connexin 43 to promote loss of gap junctions

Regulation of gap junction intercellular communication by connexin ubiquitination: physiological and pathophysiological implications

Contact Info

Product

Resources

About