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.
Department of Biochemistry, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Hanjun
H
Guan
Patricia F
PF
Maness
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