Skip to content

NAADP Receptor Research - Patel Lab

Positions: - Research Fellow (2008-2010), Cell & Developmental Biology, UCL - Research Fellow (2002-2004), Physiology Department, UCL

PI: Dr. Sandip Patel

Overview

Characterization of NAADP (nicotinic acid adenine dinucleotide phosphate) receptors and their role in lysosomal calcium signaling.

2008-2010: Lysosomal Calcium in Aging

Investigated the role of lysosomal calcium signaling in aging and disease in cultured neurons. Focus on two-pore channels (TPC1 and TPC2) as NAADP-sensitive calcium release channels.

2002-2004: NAADP Receptor Characterization

Characterized calcium-channel proteins in sea urchin eggs, establishing sea urchin as a model system for NAADP receptor studies.

Research Contributions

Lysosomal Calcium Signaling

  • Identified alterations in lysosomal calcium content in presenilin-null cells
  • Demonstrated changes in two-pore channel (TPC) expression
  • Showed effects of lysosomal proliferation on calcium homeostasis in neurons
  • Established link between lysosomal dysfunction and neurodegenerative disease

NAADP Receptor Properties

  • Characterized deviant NAADP-mediated calcium signaling upon lysosome proliferation
  • Demonstrated time-sensing properties of NAADP receptors
  • Showed requirement of phospholipids for NAADP binding
  • Developed methods for determining cellular NAADP levels
  • Characterized multiple NAADP receptor conformations
  • Successfully solubilized NAADP receptors

Techniques

Calcium Imaging

  • Confocal calcium imaging in neurons
  • Sea urchin egg calcium measurements
  • NAADP-evoked calcium release assays

Biochemistry

  • Receptor binding assays
  • Protein solubilization
  • Phospholipid interaction studies
  • NAADP quantification methods

Cell Biology

  • Primary hippocampal neuron culture
  • Lysosomal manipulation and proliferation
  • Presenilin knockout cell models

Key Findings

TPC Channels as NAADP Receptors

Work contributed to establishing two-pore channels as functional NAADP receptors, though later research showed TPC channels and TRPML1 are functionally independent organellar ion channels.

Lysosomal Dysfunction

Demonstrated that: - Lysosomal proliferation affects calcium homeostasis - Presenilin loss alters lysosomal calcium stores - TPC expression is affected by presenilin knockout - These findings have implications for neurodegenerative diseases

Publications (8 total)

  1. Yamaguchi S, Jha A, Li Q, Soyombo AA, Dickinson GD, Churamani D, Brailoiu E, Patel S, Muallem S. (2011) Transient receptor potential mucolipin 1 (TRPML1) and two-pore channels are functionally independent organellar ion channels. Journal of Biological Chemistry 286(26):22934-42. PMID: 21540176

  2. Dickinson GD, Churchill GC, Brailoiu E, Patel S. (2010) Deviant nicotinic acid adenine dinucleotide phosphate (NAADP)-mediated Ca²⁺ signaling upon lysosome proliferation. Journal of Biological Chemistry 285(18):13321-5. PMID: 20231291

  3. Churamani D, Dickinson GD, Ziegler M, Patel S. (2006) Time sensing by NAADP receptors. Biochemical Journal 397(2):313-20. PMID: 16551267

  4. Churamani D, Dickinson GD, Patel S. (2005) NAADP binding to its target protein in sea urchin eggs requires phospholipids. Biochemical Journal 386(Pt 3):497-504. PMID: 15610067

  5. Churamani D, Carrey EA, Dickinson GD, Patel S. (2004) Determination of cellular nicotinic acid-adenine dinucleotide phosphate (NAADP) levels. Biochemical Journal 380(Pt 2):449-54. PMID: 14984366

  6. Dickinson GD, Patel S. (2003) Modulation of NAADP (nicotinic acid-adenine dinucleotide phosphate) receptors by K⁺ ions: evidence for multiple NAADP receptor conformations. Biochemical Journal 375(Pt 3):805-12. PMID: 12914540

  7. Berridge G, Dickinson G, Parrington J, Galione A, Patel S. (2002) Solubilization of receptors for the novel Ca²⁺-mobilizing messenger, nicotinic acid adenine dinucleotide phosphate. Journal of Biological Chemistry 277(46):43717-23. PMID: 12223470

  8. Neely Kayala KM, Dickinson GD, Minassian A, Walls KC, Green KN, Laferla FM. (2012) Presenilin-null cells have altered two-pore calcium channel expression and lysosomal calcium. Brain Research 1489:8-16. PMID: 23103503

View all publications →

Impact

This research helped establish sea urchin eggs as a valuable model for studying NAADP receptors and contributed to understanding lysosomal calcium signaling in health and disease.

Page last updated: December 2024