2.A.3.4.1
The single high affinity plasma membrane choline transporter of 563 aas and 12 TMSs. Expression of the CTR/HNM1 gene in wild-type cells is regulated by phospholipid precursors, inositol and choline, but no such effect is seen in cells bearing mutations in the phospholipid regulatory genes INO2, INO4 and OPI1. There is no regulation by INO2 and OPI1 in the absence of a conserved decamer motif. However constructs lacking this sequence are still controlled by INO4. Other substrates of the choline permease, i.e., ethanolamine, nitrogen mustard and nitrogen half mustard do not regulate expression of CTR/HNM1 (Li and Brendel 1993). Exposing cells to increasing levels of choline results in two different regulatory mechanisms. Initial exposure to choline results in a rapid decrease in Hnm1-mediated transport activity, whereas chronic exposure results in Hnm1 degradation through an endocytic mechanism that depends on the ubiquitin ligase Rsp5 and the casein kinase 1 redundant pair Yck1/Yck2 (Fernández-Murray et al. 2013).