Gain-of-function mutations in protein kinase Cα (PKCα) may promote synaptic defects in Alzheimer’s disease

Stephanie I. Alfonso; Julia A. Callender; Basavaraj Hooli; Corina E. Antal; Kristina Mullin; Mathew A. Sherman; Sylvain E. Lesné; Michael Leitges; Alexandra C. Newton; Rudolph E. Tanzi; Roberto Malinow

doi:10.1126/scisignal.aaf6209

Research ArticleNeurodegeneration

Gain-of-function mutations in protein kinase Cα (PKCα) may promote synaptic defects in Alzheimer’s disease

Stephanie I. Alfonso¹,*,
Julia A. Callender²,³,*,
Basavaraj Hooli⁴,*,
Corina E. Antal²,³,†,
Kristina Mullin⁴,
Mathew A. Sherman⁵,
Sylvain E. Lesné⁵,
Michael Leitges⁶,
Alexandra C. Newton²,‡,
Rudolph E. Tanzi⁴,‡, and
Roberto Malinow¹,‡

¹Department of Neurosciences and Division of Biology, Section of Neurobiology, University of California, San Diego, La Jolla, CA 92093, USA.
²Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA.
³Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA.
⁴Genetics and Aging Research Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
⁵Department of Neuroscience, N. Bud Grossman Center for Memory Research and Care, and Institute for Translational Neuroscience, University of Minnesota, Minneapolis, MN 55414, USA.
⁶Biotechnology Centre of Oslo, University of Oslo, Oslo 0317, Norway.

↵‡Corresponding author. Email: anewton{at}ucsd.edu (A.C.N.); tanzi{at}helix.mgh.harvard.edu (R.E.T.); rmalinow{at}ucsd.edu (R.M.)

↵* These authors contributed equally to this work.
↵† Present address: Gene Expression Laboratory, Salk Institute, La Jolla, CA 92037, USA.

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Science Signaling 10 May 2016:
Vol. 9, Issue 427, pp. ra47
DOI: 10.1126/scisignal.aaf6209

Stephanie I. Alfonso

1Department of Neurosciences and Division of Biology, Section of Neurobiology, University of California, San Diego, La Jolla, CA 92093, USA.

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Julia A. Callender

2Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA.

3Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA.

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Basavaraj Hooli

4Genetics and Aging Research Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.

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Corina E. Antal

2Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA.

3Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA.

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Kristina Mullin

4Genetics and Aging Research Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.

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Mathew A. Sherman

5Department of Neuroscience, N. Bud Grossman Center for Memory Research and Care, and Institute for Translational Neuroscience, University of Minnesota, Minneapolis, MN 55414, USA.

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Sylvain E. Lesné

5Department of Neuroscience, N. Bud Grossman Center for Memory Research and Care, and Institute for Translational Neuroscience, University of Minnesota, Minneapolis, MN 55414, USA.

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Michael Leitges

6Biotechnology Centre of Oslo, University of Oslo, Oslo 0317, Norway.

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Alexandra C. Newton

2Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA.

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For correspondence: anewton@ucsd.edu tanzi@helix.mgh.harvard.edu rmalinow@ucsd.edu

Rudolph E. Tanzi

4Genetics and Aging Research Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.

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For correspondence: anewton@ucsd.edu tanzi@helix.mgh.harvard.edu rmalinow@ucsd.edu

Roberto Malinow

1Department of Neurosciences and Division of Biology, Section of Neurobiology, University of California, San Diego, La Jolla, CA 92093, USA.

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For correspondence: anewton@ucsd.edu tanzi@helix.mgh.harvard.edu rmalinow@ucsd.edu

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Gain-of-function mutations in protein kinase Cα (PKCα) may promote synaptic defects in Alzheimer’s disease

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