Related Experiment Video

Updated: Aug 19, 2025

Rab10 Phosphorylation Detection by LRRK2 Activity Using SDS-PAGE with a Phosphate-binding Tag
08:55

Rab10 Phosphorylation Detection by LRRK2 Activity Using SDS-PAGE with a Phosphate-binding Tag

Published on: December 14, 2017

15.3K

Disrupted in renal carcinoma 2 (DIRC2/SLC49A4) is an H+-driven lysosomal pyridoxine exporter

Shogo Akino1, Tomoya Yasujima2, Takahiro Yamashiro1

  • 1Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan.

Life Science Alliance
|December 1, 2022
PubMed

Insights

Disrupted in renal carcinoma 2 (DIRC2) functions as a proton-driven lysosomal pyridoxine exporter. Its overexpression reduces cellular vitamin B6, while its suppression increases it, impacting renal cancer development.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Disrupted in renal carcinoma 2 (DIRC2), also known as SLC49A4, is linked to renal cancer.
  • Its precise molecular function as a lysosomal metabolite transporter remains undefined.
  • Understanding DIRC2's role is crucial for insights into renal cancer pathogenesis.

Purpose of the Study:

  • To elucidate the molecular function of human DIRC2.
  • To investigate DIRC2's role in pyridoxine (vitamin B6) transport.
  • To determine DIRC2's localization and transport mechanism.

Main Methods:

  • Utilized a recombinant DIRC2-AA mutant localized to the plasma membrane.
  • Performed transient expression studies in COS-7 and HEK293 cells.
  • Employed knockdown experiments in Caco-2 cells and analyzed pyridoxine uptake.

Main Results:

  • DIRC2-AA facilitated proton-coupled pyridoxine uptake under acidic conditions.
  • Overexpression of DIRC2 reduced cellular pyridoxine accumulation.
  • Knockdown of endogenous DIRC2 increased cellular and lysosomal pyridoxine accumulation.

Conclusions:

  • DIRC2 acts as an H+-driven lysosomal pyridoxine exporter.
  • DIRC2 regulates intracellular pyridoxine levels, influencing lysosomal storage.
  • Findings provide novel insights into DIRC2's function and potential role in disease.

More Related Videos

Assay to Measure Nucleocytoplasmic Transport in Real Time within Motor Neuron-like NSC-34 Cells08:53

Assay to Measure Nucleocytoplasmic Transport in Real Time within Motor Neuron-like NSC-34 Cells

Published on: May 16, 2017

8.8K
Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease09:34

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

Published on: April 4, 2018

33.9K

Related Concept Videos

Lysosomal Hydrolases01:22

Lysosomal Hydrolases

Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
3.9K
Renal Tubule and Collecting Duct01:24

Renal Tubule and Collecting Duct

The renal tubule is divided into three parts: the proximal convoluted tubule (PCT), the Loop of Henle (LOH), and the distal convoluted tubule (DCT).
Proximal Convoluted Tubule (PCT):
The PCT is the initial segment of the renal tubule, extending from the Bowman's capsule that encloses the glomerulus. Its convoluted structure and microvilli-lined cells increase the surface area for reabsorption. The PCT reabsorbs glucose, amino acids, sodium, and water from the filtrate, ensuring essential...
1.3K
Nuclear Export01:42

Nuclear Export

The nucleus restricts several proteins within and allows others to pass. The restricted proteins possess a nuclear retention sequence or NRS, anchoring them to the nuclear lamins and preventing their transport to the cytosol. The non-restricted proteins, after their synthesis, are transported to their site of action, such as the cytosol or other organelles, with the help of nuclear export signals or NES.
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
3.7K
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.2K
Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
3.8K
Renal Corpuscle01:20

Renal Corpuscle

The glomerulus and Bowman's capsule are two essential components of the nephron, which is the functional unit of the kidney. These microscopic structures play a critical role in the process of blood filtration to produce urine.
Glomerulus: Structure and Function
The glomerulus is a tiny, intricate network of capillaries located at the beginning of the nephron. It's enveloped by the Bowman's capsule and receives its blood supply from an afferent arteriole, which divides into numerous...
3.0K