Ubiquitination within the membrane-proximal ezrin-radixin-moesin (ERM)-binding region of the L1 cell adhesion molecule

The dynamic turnover of the L1 cell adhesion molecule to and from the plasma membrane that is mediated through exo-and endocytic trafficking is central to axon outgrowth. Although the ubiquitination of L1 in response to incubation with an L1 antibody that mimics L1-L1 homophilic binding has been previously shown, the endocytic trafficking pathway of the ubiquitinated L1 destined for degradation is yet unclear. I have recently shown that the ubiquitinated L1 is endocytosed by Rabex-5, which is an ubiquitin-binding protein and guanine nucleotide exchange factor for Rab5, into early endosomes from the plasma membrane. Here, I speculate on the putative ubiquitination site within the membrane-proximal ezrin-binding motif in the cytoplasmic domain of L1 and discuss the regulatory role of this motif in the competition between ubiquitination and the binding of ezrin prior to L1 internalization.