Université de Bordeaux
BrainConf: Synaptic Plasticity27-30 September, 2022 - Bordeaux

Johannes W. Hell

Johannes W. Hell, Department of Pharmacology, University of California at Davis, USA


Calcium/calmodulin - sensitive anchoring of PSD-95 and AMPARs by alpha-actinin in spines    


Calcium/Calmodulin-sensitive anchoring of PSD-95 and AMPARs by alpha-Actinin in SPines  

Lucas Matt1, Karam Kim1, Anne E. Hergarden1, Tommaso Patriarchi1, Dhrubajyoti Chowdhury1, eter B. Henderson1, Yonghong Zhang3, James B. Ames3, Mary C. Horne1,2, and Johannes W. Hell1,2 #


1 Department of Pharmacology, University of California, Davis, USA;

2 Department of Pharmacology, University of Iowa, Iowa City, USA;

3 Department of Chemistry, University of California, Davis, USA;

We find that the F-actin binding protein α-actinin binds to the very N-terminus of PSD-95 and that knock-down (kd) of α-actinin phenocopies kd of PSD-95. Mutating residues in PSD-95 or α-actinin that are important for their interactions impairs in parallel PSD-95 binding to α-actinin and postsynaptic localization of PSD-95 and AMPARs. Furthermore, postsynaptic Ca influx induces binding of Calcium/calmodulin to the N-terminus of PSD-95, which displaces alpha-actinin from this binding site and leads to a reduction of PSD-95 from postsynaptic sites. This mechanism is important for homeostatic synaptic scaling down in response to increased synaptic activity by blockage of GAGA receptors. These results identify α-actinin as a critical anchor for PSD-95 and thereby AMPARs.



1987    Diplom (M.S.) in Biochemistry, University of Tübingen, Germany
1990    Promotion (Ph.D.) in Biochemistry (R. Jahn), University of Munich, Germany            
1991-1995  Postdoctoral Fellow with Dr. W. A. Catterall, University of Washington, Seattle            
1995-2001  Assistant Professor, Department of Pharmacology, University of Wisconsin, Madison
2001-2009  Professor, Department of Pharmacology, University of Iowa, Iowa City
2009-present  Professor and Vice Chair, Department of Pharmacology, UC Davis
2016-present  Director and T32 PI, Predoctoral Training in Pharmacological Sciences  

Research Interest

My research is focused on the molecular mechanisms that regulate glutamate receptors and the L-type Ca channel Cav1.2 at the glutamatergic synapse in the brain and how those mechanisms related to synaptic plasticity. These mechanisms include signaling by norepinephrine, which is important for understanding long-term potentiation, learning, and especially attention. This signaling is affected in Alzheimer’s disease and ADHD, two areas that our lab investigates on the molecular, cellular, electrophysiological and behavioral level. We perform cutting edge biochemical and structural analysis which, superresolution microscopy, cell attached single channel and whole cell recordings of electric activity and synaptic transmission, LTP and LTD, and behavioral tests for attention and learning including working memory.