Page 58 - F. Cell biology

[F. Cell biology-34]

Prominin-1 radixin axis controls the trafficking of various bile

canaliculi proteins by regulating PKA activity in hepatocytes

Young Jae Kwon¹˙#, Hyun Lee¹˙#, Young-Gyu Ko¹˙*

¹Life science, Korea university, seoul 02841, Korea

Hepatocyte is highly polarized epithelial cells with apical canalicular domains designed for bile production in liver.
The bile canalicular domain of hepatocytes contains several membrane transporters containing bile salt export
pump (Bsep, Abcb11) and multidrug resistance proteins (Mdr1, Abcb1). We observed that the Prominin-1(prom1,

also known as CD-133), pentaspan transmembrane glycoprotein, is primarily localized at the canalicular membrane

of hepatocytes. When we investigated phenotype during lithogenic diet model in Prom1+/+ and Prom1-/- mice,
Prom1 deficiency showed a more aggravated phenotype by lithogenic-induced cholestatic liver injury. Furthermore,
the canalicular localization of proteins was significantly reduced in Prom1-/- mice. Because some canaliculi

membrane transporters are recruited from intracellular pools to the bile canaliculi by PKA(Protein kinase A) signaling,
we investigated the relevance of this machinery in lithogenic diet induced events. As a result, The prom1 deficiency

inhibited cAMP dependent protein kinase A(PKA) activation and migration of various transporters to the canalicular
domain. Based on these results, we conclude that Prom1 regulates the transport of various membrane transporters

to canaliculi by PKA signaling in liver injury condition.