Genetic Inactivation of Two-Pore Channel 1 Impairs Spatial Learning and Memory

Robert Theodor Mallmann,Norbert Klugbauer

doi:10.1007/s10519-020-10011-1

Robert Theodor Mallmann, Norbert Klugbauer

Open Access

https://doi.org/10.1007/s10519-020-10011-1

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Journal: Behavior Genetics	Publication Date: Sep 5, 2020
Citations: 8	License type: open-access

Affiliation: University of Freiburg

Abstract

Two-pore channels (TPCs) constitute a small family of cation channels that are localized in membranes of endosomal and lysosomal compartments. Although their roles for vesicular fusion and endolysosomal trafficking have been investigated, our knowledge on their expression pattern and higher order functions in the murine brain is still limited. Western blot analysis indicated a broad expression of TPC1 in the neocortex, cerebellum and hippocampus. In order to investigate the consequences of the genetic inactivation of TPC1, we performed a set of behavioural studies with TPC1−/− mice. TPC1−/− mice were analysed for an altered motor coordination and grip-strength, exploratory drive and anxiety as well as learning and memory. TPC1−/− mice did not show any differences in their exploratory drive or in their anxiety levels. There were also no differences in spontaneous activity or motor performance. However, the Morris water maze test uncovered a deficit in spatial learning and memory in TPC1−/− mice.

Highlights

Two-pore channels (TPCs) constitute a small family of intracellularly localized cation channels
There was no compensatory upregulation of TPC2 in TPC1-deficient mice, indicating that expression of TPC2 is independent of TPC1
We took advantage of our TPC1 knock out mice to achieve novel insights into higher order functions of this ion channel

Summary

Introduction

Two-pore channels (TPCs) constitute a small family of intracellularly localized cation channels. Only two TPCs have been identified, though, other species express three functional tpc-genes. TPCs form intermediates between one-domain TRP and four-domain voltage gated N a+ or Ca2+ channels. TPCs are found in membranes of small and acidic intracellular organelles such as endosomes and lysosomes. Within these compartments, they show a smooth transition from TPC1.

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