Presentation Title

Genetic interactions among LRRK2, VPS35, and Rme-8 in a Drosophila model of Parkinson’s disease

Faculty Mentor

Katrina Venderova

Start Date

17-11-2018 8:30 AM

End Date

17-11-2018 10:30 AM

Location

CREVELING 13

Session

POSTER 1

Type of Presentation

Poster

Subject Area

biological_agricultural_sciences

Abstract

Autophagy is a conserved cellular degradation process essential for intracellular waste disposal and energy balance. Although dysregulation of autophagy seems associated with Parkinson’s disease (PD), PD’s pathogenesis remains largely unknown. Mutations in the Leucine-rich repeat kinase 2 (LRRK2) gene are the most common genetic of PD; thus, LRRK2 mutations are commonly used in genetic models of PD. The retromer, a protein complex that consists of a heterodimer of sorting nexin (Snx) and the cargo recognition VPS26-VPS29-VPS35 heterotrimer, is involved in transmembrane protein sorting and endosomal recycling, and is necessary for the autophagy process to proceed. The lab of Dr. Venderova previously demonstrated that VPS35 overexpression rescues phenotypes of the pathogenic mutant LRRK2, indicating that LRRK2 and VPS35 share a common pathway. To further study this interaction, our lab focused on Rme-8, a protein that physically associates with the Snx dimer of the retromer, to further map this pathway for potential identification of novel pharmacological targets. Specifically, we investigated the role of Rme-8 in rescuing mutant LRRK2 by VPS35 overexpression through genetic crosses in a Drosophila model, aiming to further unveil the genetic interactions among LRRK2, VPS35, and Rme-8. We show that Rme-8 is required for rescue of the mutant LRRK2 eye and locomotor phenotypes by VPS35.

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Nov 17th, 8:30 AM Nov 17th, 10:30 AM

Genetic interactions among LRRK2, VPS35, and Rme-8 in a Drosophila model of Parkinson’s disease

CREVELING 13

Autophagy is a conserved cellular degradation process essential for intracellular waste disposal and energy balance. Although dysregulation of autophagy seems associated with Parkinson’s disease (PD), PD’s pathogenesis remains largely unknown. Mutations in the Leucine-rich repeat kinase 2 (LRRK2) gene are the most common genetic of PD; thus, LRRK2 mutations are commonly used in genetic models of PD. The retromer, a protein complex that consists of a heterodimer of sorting nexin (Snx) and the cargo recognition VPS26-VPS29-VPS35 heterotrimer, is involved in transmembrane protein sorting and endosomal recycling, and is necessary for the autophagy process to proceed. The lab of Dr. Venderova previously demonstrated that VPS35 overexpression rescues phenotypes of the pathogenic mutant LRRK2, indicating that LRRK2 and VPS35 share a common pathway. To further study this interaction, our lab focused on Rme-8, a protein that physically associates with the Snx dimer of the retromer, to further map this pathway for potential identification of novel pharmacological targets. Specifically, we investigated the role of Rme-8 in rescuing mutant LRRK2 by VPS35 overexpression through genetic crosses in a Drosophila model, aiming to further unveil the genetic interactions among LRRK2, VPS35, and Rme-8. We show that Rme-8 is required for rescue of the mutant LRRK2 eye and locomotor phenotypes by VPS35.