biostudies-literatureUnknown67(9)Van den Abbeele ARNA interference has tremendously advanced our understanding of gene function but recent reports have exposed undesirable side-effects. Recombinant Camelid single-domain antibodies (VHHs) provide an attractive means for studying protein function without affecting gene expression. We raised VHHs against gelsolin (GsnVHHs), a multifunctional actin-binding protein that controls cellular actin organization and migration. GsnVHH-induced delocalization of gelsolin to mitochondria or the nucleus in mammalian cells reveals distinct subpopulations including free gelsolin and actin-bound gelsolin complexes. GsnVHH 13 specifically recognizes Ca(2+)-activated gelsolin (K (d) approximately 10 nM) while GsnVHH 11 binds gelsolin irrespective of Ca(2+) (K (d) approximately 5 nM) but completely blocks its Cellular and molecular life sciences : CMLS1519-35https://www.ebi.ac.uk/biostudies/studies/S-EPMC11115616biostudies-literatureA llama-derived gelsolin single-domain antibody blocks gelsolin-G-actin interaction.PMC11115616Steyaert JDe Corte VSoror SHDe Clercq SVan den Abbeele AVandekerckhove JGettemans JDe Ganck AVan Loo BSrinivasan VfalseA llama-derived gelsolin single-domain antibody blocks gelsolin-G-actin interaction.RNA interference has tremendously advanced our understanding of gene function but recent reports have exposed undesirable side-effects. Recombinant Camelid single-domain antibodies (VHHs) provide an attractive means for studying protein function without affecting gene expression. We raised VHHs against gelsolin (GsnVHHs), a multifunctional actin-binding protein that controls cellular actin organization and migration. GsnVHH-induced delocalization of gelsolin to mitochondria or the nucleus in mammalian cells reveals distinct subpopulations including free gelsolin and actin-bound gelsolin complexes. GsnVHH 13 specifically recognizes Ca(2+)-activated gelsolin (K (d) approximately 10 nM) while GsnVHH 11 binds gelsolin irrespective of Ca(2+) (K (d) approximately 5 nM) but completely blocks its 2010-01-01T00:00:00Z2010 May2026-06-03T06:46:53.633Z2026-05-29T03:05:57.02ZS-EPMC111156162014075010.1007/s00018-010-0266-1