Recent advances in the molecular biology of metazoan polyamine transport

Abstract

Very limited molecular knowledge exists about the identity and protein components of the ubiquitous polyamine transporters found in animal cells. However, a number of reports have been published over the last 5 years on potential candidates for metazoan polyamine permeases. We review the available evidence on these putative polyamine permeases, as well as establish a useful "identikit picture" of the general polyamine transport system, based on its properties as found in a wide spectrum of mammalian cells. Any molecular candidate encoding a putative "general" polyamine permease should fit that provided portrait. The current models proposed for the mechanism of polyamine internalization in mammalian cells are also briefly reviewed.

Fig. 1

Putative models for the mechanism of polyamine accumulation and sequestration into vesicles in mammalian cells. a Model adapted from (Soulet et al. 2004) illustrating a two-step mechanism for polyamine transport and vesicular sequestration. b Model adapted from (Belting et al. 2003) proposing that spermine first binds to heparan sulfate groups in glypican-1 and is subsequently internalized and freed from glypican via NO-mediated oxidation. NOS2 nitric oxide synthase-2, PA polyamines, PUT putrescine, SPM spermine. c Model based on (Uemura et al. 2010) suggesting a caveolin-1-dependent internalization of polyamines bound to a putative “polyamine receptor”. Putrescine (but not higher polyamines) might exit from the vesicles via the SLC3A2-bound diamine exporter