Characterization of a mutant form of human apolipoprotein B (Thr26-Tyr27del) associated with familial hypobetalipoproteinemia

Angelo Baldassare Cefalu', Maurizio Averna, Lucia Magnolo, Sebastiano Calandra, Patrizia Tarugi, Zemin Yao, Davide Noto

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


We have previously identified a deletion mutant of human apoB [apoB (Thr26-Tyr27del)] in a subject with primary hypobetalipoproteinemia. The present study determined the effect of Thr26-Tyr27del mutation on apoB secretion using transfected McA-RH7777 cells. Transient or stable transfection of apoB-48 containing the Thr26-Tyr27del mutation showed drastically reduced secretion of the mutant as compared to wild-type apoB-48. No lipoproteins containing the mutant apoB-48 were secreted into the medium. Incubation of transfected cells in a lipid-rich medium in the presence of cycloheximide showed rapid turnover of cell-associated mutant apoB-48 as compared to that of wild-type apoB-48. Immunofluorescence experiments showed that the mutant apoB-48 was mostly localized in the endoplasmic reticulum. Treatment with the proteasomal inhibitor MG132 markedly attenuated the turnover of cell-associated mutant apoB-48, whereas treatment with inhibitors of autophagosomal/lysosomal function (e.g. 3-MA or ammonium chloride) had no effect. Taken together, these results indicated that the defective secretion of the Thr26-Tyr27del mutant was associated with increased intracellular degradation of apoB through the proteasome-dependent pathway.
Original languageEnglish
Pages (from-to)371-379
Number of pages9
Publication statusPublished - 2016

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Characterization of a mutant form of human apolipoprotein B (Thr26-Tyr27del) associated with familial hypobetalipoproteinemia'. Together they form a unique fingerprint.

Cite this