Cytokinesis defines a spatial landmark for hepatocyte polarization and apical lumen formation

Abstract

By definition, all epithelial cells have apical-basal polarity, but it is unclear how epithelial polarity is acquired and how polarized cells engage in tube formation. Here, we show that hepatocyte polarization is linked to cytokinesis using the rat hepatocyte cell line Can 10. Before abscission, polarity markers are delivered to the site of cell division in a strict spatiotemporal order. Immediately after abscission, daughter cells remain attached through a unique disc-shaped structure, which becomes the site for targeted exocytosis, resulting in the formation of a primitive bile canaliculus. Subsequently, oriented cell division and asymmetric cytokinesis occur at the bile canaliculus midpoint, resulting in its equal partitioning into daughter cells. Finally, successive cycles of oriented cell division and asymmetric cytokinesis lead to the formation of a tubular bile canaliculus, which is shared by two rows of hepatocytes. These findings define a novel mechanism for cytokinesis-linked polarization and tube formation, which appears to be broadly conserved in diverse cell types.

Aberrant Activation of Atypical Protein Kinase C in Carbon Tetrachloride–Induced Oxidative Stress Provokes a Disturbance of Cell Polarity and Sealing of Bile Canalicular Lumen

“…8 Par-3 plays a critical role in regulating centrosome orientation for bile canaliculus formation, but not its maintenance, in cultured rat hepatocytes. 11 In this study, we found that Par-3eaPKC may play a crucial role in the maintenance of the bile canalicular lumen. This finding would provide novel insights into the understanding of maintenance and disturbance of the bile canalicular lumen.…”

“…8,10 A recent report revealed 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 that knockdown of Par-3 prevented de novo bile canaliculus formation in an in vitro culture system. 11 Selective depletion of aPKCl in mouse podocytes results in the disassembly of intercellular junctions (slit diaphragms) and focal segmental glomerulosclerosis (FSGS). 12 FSGS pathogenic pathways may involve oxidative stress and inflammation associated with mononuclear leukocyte recruitment.…”

Estrogen-Related Receptor α (ERRα) and ERRγ Are Essential Coordinators of Cardiac Metabolism and Function

“…MEFs were fixed with methanol for 10 min at Ϫ20°C. After incubation with an ATP5b antibody (A21351; Life Technologies) and fluorescence-labeled secondary antibody (Jackson ImmunoResearch), the mitochondrial morphology was imaged using a Zeiss LSM710 confocal microscope with a 63ϫ oil immersion lens (28). For mitochondrial size and perimeter analysis, 20 to 25 images per group were used.…”

Rab GTPases and cell division

“…Significantly, recent studies have demonstrated that the formation of apico-basal polarity and initiation as well as formation of the apical lumen is coupled to cell division. 36,37 Additionally, it was shown that in 3D tissue culture systems the location of the cytokinetic bridge between the first 2 daughter cells is the first symmetrybreaking event that establishes the location of the apical membrane initiation site (AMIS), and therefore, the positioning of the newly forming apical lumen. 36,38 Consequently, Rab11 and Rab35 are now emerging as regulators of both cell division and epithelial cell polarization.…”

“…Then, centrosomes migrate close to the disk-shaped tight junctions between the daughter cells to nucleate microtubules that target the Exocyst complexdependent transport and targeting, leading to canaliculus formation. 37 Which Rab GTPase(s) are involved in this process remains to be determined, however considering that the Exocyst complex binds Rab11, it is likely that Rab11GTPase is also involved in canaliculus genesis.…”