Presentation Title

Single Nucleotide Polymorphisms in the TMEM163 gene

Faculty Mentor

Dr. Math P. Cuajungco

Start Date

17-11-2018 9:45 AM

End Date

17-11-2018 10:00 AM

Location

C162

Session

Oral 2

Type of Presentation

Oral Talk

Subject Area

biological_agricultural_sciences

Abstract

Mucolipidosis type IV (MLIV) is a neurodegenerative disease caused by mutations or deletions within the Mucolipin-1 (MCOLN1) gene, which encodes the TRPML1 protein. Abnormal zinc accumulation has been found in the brain tissues of MLIV mouse model and cells from MLIV patients. We found transmembrane-163 protein (TMEM163) as an interaction partner for TRPML1. We found both proteins to co-localize on the plasma membrane and lysosomal compartments and suggested both play a role in intracellular zinc homeostasis. TMEM163 is predicted to have six transmembrane domains (TMD). The single nucleotide polymorphism database from the National Center for Biotechnology Information website was used to identify specific nucleotide sequence variations within the TMEM163 gene. We then used bioinformatics to predict the topology of TMEM163 protein and found that some SNP-associated amino acid substitutions are located in areas of the protein that could affect post-translational modification and change its structure and function. Here, we show for the first time that human TMEM163 is a zinc-efflux transporter as demonstrated by TMEM163-expressing human embryonic kidney (HEK)-293 cells pre-loaded with zinc chloride (10 μM) and zinc pyrithione (1 μM) exhibited a marked increase in extracellular zinc levels using the membrane-impermeable, zinc-specific FluoZin-3 AM dye. We found that the function of TMEM163 is abolished when a non-synonymous amino acid mutation is introduced within the protein supporting our observations that TMEM163 is a zinc-efflux transporter. Thus, understanding the nature of TMEM163-TRPML1 interaction is necessary to further support our findings of zinc dyshomeostasis in MLIV cells.

Summary of research results to be presented

Here, we show for the first time that human TMEM163 is a zinc-efflux transporter as demonstrated by TMEM163-expressing human embryonic kidney (HEK)-293 cells pre-loaded with zinc chloride (10 μM) and zinc pyrithione (1 μM) exhibited a marked increase in extracellular zinc levels using the membrane-impermeable, zinc-specific FluoZin-3 AM dye.

This document is currently not available here.

Share

COinS
 
Nov 17th, 9:45 AM Nov 17th, 10:00 AM

Single Nucleotide Polymorphisms in the TMEM163 gene

C162

Mucolipidosis type IV (MLIV) is a neurodegenerative disease caused by mutations or deletions within the Mucolipin-1 (MCOLN1) gene, which encodes the TRPML1 protein. Abnormal zinc accumulation has been found in the brain tissues of MLIV mouse model and cells from MLIV patients. We found transmembrane-163 protein (TMEM163) as an interaction partner for TRPML1. We found both proteins to co-localize on the plasma membrane and lysosomal compartments and suggested both play a role in intracellular zinc homeostasis. TMEM163 is predicted to have six transmembrane domains (TMD). The single nucleotide polymorphism database from the National Center for Biotechnology Information website was used to identify specific nucleotide sequence variations within the TMEM163 gene. We then used bioinformatics to predict the topology of TMEM163 protein and found that some SNP-associated amino acid substitutions are located in areas of the protein that could affect post-translational modification and change its structure and function. Here, we show for the first time that human TMEM163 is a zinc-efflux transporter as demonstrated by TMEM163-expressing human embryonic kidney (HEK)-293 cells pre-loaded with zinc chloride (10 μM) and zinc pyrithione (1 μM) exhibited a marked increase in extracellular zinc levels using the membrane-impermeable, zinc-specific FluoZin-3 AM dye. We found that the function of TMEM163 is abolished when a non-synonymous amino acid mutation is introduced within the protein supporting our observations that TMEM163 is a zinc-efflux transporter. Thus, understanding the nature of TMEM163-TRPML1 interaction is necessary to further support our findings of zinc dyshomeostasis in MLIV cells.