Endocytosis is one of the main pathways for cells to take up extracellular molecules including nutrients, receptors, and cellular penetrating peptides (CPPs). Endosome dynamics are tightly controlled by the sequential recruitment of various endosomal proteins and lipids. Rab5 and Rab7, members of the GTPase Rab family, are known to be key regulators in the canonical endocytic pathway that moves endocytosed material to lysosomes. However, there lacks a consensus on the underlying mechanisms of endocytosis for CPPs, polyamines, and other cationic molecules.
In a recent publication in Cell Reports, E. Trofimenko et al. identify a separate Rab14-dependent endosomal pathway for CPPs, homeodomains (HDs), and polyamines. They studied the uptake of fluorescently labeled CPPs, HDs, and polyamines into HeLa cells and their colocalization with early and late endosomal markers. The polyamine spermine was labeled with CF®405M, CF®488A, CF®647, and CF®594 using Mix-n-Stain™ Small Ligand Labeling Kits. Results show that endocytosis of CPPs, HDs, and polyamines follow a Rab5-independent and Rab14-dependent route. In addition, the endosomal pathway of CPPs ends in non-degradative lysosomes, further suggesting that this form of endocytosis is distinct from Rab5-dependent pathways. The authors claim that this represents a previously undescribed endosomal maturation pathway, which has potential implications for studying the infection route of certain viruses such as Herpes Simplex Virus 1, SARS-CoV, and some influenza A strains, which appear to skip early Rab5-positive endosomes.
Trofimenko, E., Homma, Y., Fukuda, M., & Widmann, C. (2021). The endocytic pathway taken by cationic substances requires Rab14 but not Rab5 and Rab7. Cell Reports, 37(5), 109945. https://doi.org/10.1016/j.celrep.2021.109945