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Genes Dev. 2019 Mar 1;33(5-6):365-376. doi: 10.1101/gad.320077.118. Epub 2019 Feb 26.

Synaptotagmin-11 mediates a vesicle trafficking pathway that is essential for development and synaptic plasticity.

Author information

1
Department of Neuroscience, Scripps Research, La Jolla, California 92037, USA.
2
The Dorris Neuroscience, Scripps Research, La Jolla, California 92037, USA.
3
Department of Molecular Medicine, Scripps Research, La Jolla, California 92037, USA.
4
Department of Neuroscience, University of Texas Southwestern Medical Center at Dallas, Dallas 75235, Texas, USA.
5
Department of Molecular and Cellular Physiology, Stanford University, Palo Alto, California 94035, USA.
#
Contributed equally

Abstract

Synaptotagmin-11 (Syt11) is a Synaptotagmin isoform that lacks an apparent ability to bind calcium, phospholipids, or SNARE proteins. While human genetic studies have linked mutations in the Syt11 gene to schizophrenia and Parkinson's disease, the localization or physiological role of Syt11 remain unclear. We found that in neurons, Syt11 resides on abundant vesicles that differ from synaptic vesicles and resemble trafficking endosomes. These vesicles recycle via the plasma membrane in an activity-dependent manner, but their exocytosis is slow and desynchronized. Constitutive knockout mice lacking Syt11 died shortly after birth, suggesting Syt11-mediated membrane transport is required for survival. In contrast, selective ablation of Syt11 in excitatory forebrain neurons using a conditional knockout did not affect life span but impaired synaptic plasticity and memory. Syt11-deficient neurons displayed normal secretion of fast neurotransmitters and peptides but exhibited a reduction of long-term synaptic potentiation. Hence, Syt11 is an essential component of a neuronal vesicular trafficking pathway that differs from the well-characterized synaptic vesicle trafficking pathway but is also essential for life.

KEYWORDS:

development; membrane trafficking; memory; mouse genetics; neuron; secretion; synaptic plasticity; synaptotagmin

PMID:
30808661
DOI:
10.1101/gad.320077.118

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