Scaffold protein X11α interacts with kalirin-7 in dendrites and recruits it to Golgi outposts.
Pyramidal neurons in the mammalian forebrain receive their synaptic inputs through their dendritic trees, and dendritic spines are the sites of most excitatory synapses. Dendritic spine structure is important for brain development and plasticity. Kalirin-7 is a guanine nucleotide-exchange factor for the small GTPase Rac1 and is a critical regulator of dendritic spine remodeling. The subcellular localization of kalirin-7 is thought to be important for regulating its function in neurons. A yeast two-hybrid screen has identified the adaptor protein X11α as an interacting partner of kalirin-7. Here, we show that kalirin-7 and X11α form a complex in the brain, and this interaction is mediated by the C terminus of kalirin-7. Kalirin-7 and X11α co-localize at excitatory synapses in cultured cortical neurons. Using time-lapse imaging of fluorescence recovery after photobleaching, we show that X11α is present in a mobile fraction of the postsynaptic density. X11α also localizes to Golgi outposts in dendrites, and its overexpression induces the removal of kalirin-7 from spines and accumulation of kalirin-7 in Golgi outposts. In addition, neurons overexpressing X11α displayed thinner spines. These data support a novel mechanism of regulation of kalirin-7 localization and function in dendrites, providing insight into signaling pathways underlying neuronal plasticity. Dissecting the molecular mechanisms of synaptic structural plasticity will improve our understanding of neuropsychiatric and neurodegenerative disorders, as kalirin-7 has been associated with schizophrenia and Alzheimer disease.
From the Departments of Physiology and.
Kelly A
KA
Jones
the Interdepartmental Neuroscience Graduate Program, Northwestern University, Chicago, Illinois 60611, and.
Andrew G
AG
Eng
the Department of Neuroscience and Centre for the Cellular Basis of Behaviour, The James Black Centre, Institute of Psychiatry, King's College London, London SE5 9NU, United Kingdom.
Pooja
P
Raval
From the Departments of Physiology and the Department of Neuroscience and Centre for the Cellular Basis of Behaviour, The James Black Centre, Institute of Psychiatry, King's College London, London SE5 9NU, United Kingdom deepak.srivastava@kcl.ac.uk.
Deepak P
DP
Srivastava
From the Departments of Physiology and Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, p-penzes@northwestern.edu.
Peter
P
Penzes
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D003712:Dendrites / Q000378:metabolism*; D049229:Dendritic Spines / Q000378:metabolism; D036681:Fluorescence Recovery After Photobleaching; D006056:Golgi Apparatus / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D008959:Models, Neurological; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism; D011485:Protein Binding; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000378:metabolism; D059008:Time-Lapse Imaging; D020798:Two-Hybrid System Techniques; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C513071:Apba1 protein, rat; D020662:Guanine Nucleotide Exchange Factors; C102365:Kalrn protein, rat; D008565:Membrane Proteins; D020830:rac1 GTP-Binding Protein
Dendritic Spine; Neurobiology; Neuron; Neuroscience; Small GTPase; Synapse