Abstract
Lamellipodin (Lpd) functions as an important signalling integrator downstream of growth factor and axon guidance receptors. Mechanistically, Lpd promotes actin polymerization by interacting with F-actin and the actin effectors Ena/VASP proteins and the SCAR/WAVE complex. Thereby, Lpd supports lamellipodia protrusion, cell migration and endocytosis. In the mammalian central nervous system, Lpd contributes to neuronal morphogenesis, neuronal migration during development and its C. elegans orthologue MIG-10 also supports synaptogenesis. However, the consequences of loss of Lpd in the CNS on behaviour are unknown. In our current study, we crossed our Lpd conditional knockout mice with a mouse line expressing Cre under the CNS specific Nestin promoter to restrict the genetic ablation of Lpd to the central nervous system. Detailed behavioural analysis of the resulting Nestin-Cre-Lpd knockout mouse line revealed a specific behavioural phenotype characterised by hyperactivity and increased anxiety.
Highlights
Lamellipodin (Lpd; official HGNC gene symbol: RAPH1) is a vertebrate member of the MRL (MIG-10, RIAM, Lamellipodin) protein family which includes RIAM in vertebrates, MIG-10 in C. elegans and Pico in Drosophila[1,2,3,4,5]
The available evidence suggests that Lpd promotes neuronal morphogenesis, neuronal migration during CNS development in mice and synaptogenesis in C. elegans
We crossed our Lpd conditional mice with a mouse line expressing Cre under the CNS specific Nestin promoter to restrict the genetic ablation to the central nervous system
Summary
Lamellipodin (Lpd; official HGNC gene symbol: RAPH1) is a vertebrate member of the MRL (MIG-10, RIAM, Lamellipodin) protein family which includes RIAM in vertebrates, MIG-10 in C. elegans and Pico in Drosophila[1,2,3,4,5]. Lpd localises to the very edge of lamellipodia, the tips of filopodia, and to clathrin coated pits[1, 6] At these locations, Lpd functions as an important signalling integrator downstream of growth factor and axon guidance receptors. The available evidence suggests that Lpd promotes neuronal morphogenesis, neuronal migration during CNS development in mice and synaptogenesis in C. elegans. We previously had generated conditional knockout mice for Lpd, which we crossed to PGK-Cre general deleter mice on a pure C57BL6 background. We crossed our Lpd conditional mice with a mouse line expressing Cre under the CNS specific Nestin promoter to restrict the genetic ablation to the central nervous system. Our results revealed a specific behavioural phenotype resulting from the genetic ablation characterized by hyperactivity and increased anxiety in the open field test
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