Nhsl3, a member of the Nance-Horan Syndrome family, plays a crucial role in cell migration. The underlying molecular mechanisms of cell migration are not fully understood, and studying Nhsl3 can provide insights into this process [1].

A recent study using gene knockout cells for Nhsl3 found that Nhsl3-knockout cells are more persistent in single-cell migration compared to parental cells, while in wound healing, follower cells' ability to follow leader cells is impaired [1]. The NHSL3 locus encodes several isoforms. Proteomics was used to identify the partner repertoire of each isoform, and an AlphaFold2-based pipeline predicted direct partners and their binding sites [1]. Rescue experiments with specific isoforms demonstrated that the interaction of a long isoform with MENA/VASP proteins at cell-cell junctions is critical for collective migration, and the interaction of a short isoform with 14-3-3θ in lamellipodia is crucial for single-cell migration [1].

In conclusion, Nhsl3 regulates single and collective cell migration through distinct mechanisms. The use of gene knockout models has revealed these functions of Nhsl3 in cell migration, which may contribute to a better understanding of processes related to wound healing and potentially other physiological and pathological conditions where cell migration is involved [1].