Decreased anxiety-related behaviour but apparently unperturbed NUMB function in ligand of NUMB protein-X (LNX) 1/2 double knockout mice
| Autor: | Victoria Heimer-McGinn, Orthis Saha, Paul Young, Joan A. Lenihan, Guoping Feng, John F. Cryan |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Proteomics
0301 basic medicine Ubiquitin-Protein Ligases Central nervous system Neuroscience (miscellaneous) Nerve Tissue Proteins Anxiety Ligands LNX2 03 medical and health sciences Cellular and Molecular Neuroscience LNX1 Ubiquitin NUMB medicine Animals Mice Knockout Neurons biology Neurogenesis Intracellular Signaling Peptides and Proteins Membrane Proteins Ligand (biochemistry) Phenotype SRGAP2 030104 developmental biology medicine.anatomical_structure Neurology biology.protein Carrier Proteins ERC1/ERC2 Neuroscience LIPRIN/PPFIA Presynaptic active zone |
| Popis: | NUMB is a key regulator of neurogenesis and neuronal differentiation that can be ubiquitinated and targeted for proteasomal degradation by ligand of numb protein-X (LNX) family E3 ubiquitin ligases. However, our understanding of LNX protein function in vivo is very limited. To examine the role of LNX proteins in regulating NUMB function in vivo, we generated mice lacking both LNX1 and LNX2 expression in the brain. Surprisingly, these mice are healthy, exhibit unaltered levels of NUMB protein and do not display any neuroanatomical defects indicative of aberrant NUMB function. Behavioural analysis of LNX1/LNX2 double knockout mice revealed decreased anxiety-related behaviour, as assessed in the open field and elevated plus maze paradigms. By contrast, no major defects in learning, motor or sensory function were observed. Given the apparent absence of major NUMB dysfunction in LNX null animals, we performed a proteomic analysis to identify neuronal LNX-interacting proteins other than NUMB that might contribute to the anxiolytic phenotype observed. We identified and/or confirmed interactions of LNX1 and LNX2 with proteins known to have presynaptic and neuronal signalling functions, including the presynaptic active zone constituents ERC1, ERC2 and LIPRIN-αs (PPFIA1, PPFIA3), as well as the F-BAR domain proteins FCHSD2 (nervous wreck homologue) and SRGAP2. These and other novel LNX-interacting proteins identified are promising candidates to mediate LNX functions in the central nervous system, including their role in modulating anxiety-related behaviour. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|