Perisomatic GABAergic innervation in prefrontal cortex is regulated by ankyrin interaction with the L1 cell adhesion molecule.
The L1 adhesion molecule functions in axon growth and guidance, but a role in synaptic development of cortical inhibitory interneurons is largely unexplored. L1 mediates adhesion by engaging the actin cytoskeleton through binding the actin/spectrin adapter protein ankyrin. Loss of L1-ankyrin interaction impaired process elaboration/branching by GABAergic interneurons, including basket cells, and reduced the number of perisomatic synapses in the cingulate cortex as shown in L1 mutant mice (L1YH) with a mutation in the ankyrin-binding site, either alone or intercrossed with GAD67-enhanced green fluorescence protein reporter mice. Electron microscopy revealed that perisomatic inhibitory synapses but not excitatory synapses in the neuropil were specifically affected. In wild-type cingulate cortex, L1 colocalized with perisomatic synaptic markers, whereas L1 phosphorylation on Tyr(1229) decreased postnatally, correlating with increased ankyrin binding and synaptic development. These results suggest a novel role for L1 engagement with the actin cytoskeleton in development of inhibitory connectivity within the cingulate cortex.
Guan
Hanjun
H
Department of Biochemistry, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Maness
Patricia F
PF
D008841:Actin Cytoskeleton / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017487:Ankyrins / Q000502:physiology*; D055879:Gene Knock-In Techniques; D006179:Gyrus Cinguli / Q000378:metabolism / Q000502:physiology; D007395:Interneurons / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants; D008822:Mice, Transgenic; D019579:Neocortex / Q000166:cytology / Q000502:physiology; D039842:Neural Cell Adhesion Molecule L1 / Q000235:genetics / Q000502:physiology*; D009433:Neural Inhibition / Q000235:genetics; D017397:Prefrontal Cortex / Q000166:cytology / Q000254:growth & development / Q000502:physiology*; D017729:Presynaptic Terminals / Q000502:physiology*; D011485:Protein Binding / Q000235:genetics; D013569:Synapses / Q000235:genetics; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D017487:Ankyrins; D039842:Neural Cell Adhesion Molecule L1; D005680:gamma-Aminobutyric Acid