Xuelin Lou, PhD
- Cell Biology, Neurobiology & Anatomy
Research Areas of Interest
- Islet beta cells, Diabetes
- Super-resolution imaging, Nanoscopy
- Synapses, Neurodegeneration, Alzheimer's Disease
- Actin Cytoskeleton
- Calcium Signaling
- Diabetes Mellitus, Type 2
- Ion Channels
- Islets of Langerhans
- membrane biophysics
- Membrane Fusion
- Mice, Knockout
Methodologies and Techniques
- Beta cells
- Capacitance recording
- Electron microscopy and tomography
- Live cell imaging: spinning disk confocal, TIRFM, FRET
- Molecular Biology
- mouse genetics
- Patch-Clamp Techniques
- sub-cellular optogenetics
- Super-resolution microscopy (PALM, dSTORM, SIM, STED)
We are interested in neural communication in the brain. We study vesicle trafficking in neurons and neuroendocrine cells in health and disease. Our work is at the interface of neuroscience, cell biology, and biophysics. It is closely relevant to several human diseases that currently have no cure. Multiple cutting-edge approaches are utilized and developed in our study, including live-cell imaging (TIRF/Confocal), PALM/d-STORM, optogenetics, patch-clamp, and mouse models.
Synapses and Synaptopathy
Synapse is the corner stone for brain function. Synaptic transmission is essential for neural circuit to function properly. Accordingly, synaptopathy (a disruption of synaptic structure and/or function) has been increasingly implicated in numerous brain disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease, epilepsy, autism, and schizophrenia. We study fundamental aspects of presynaptic terminals: mechanisms underlying transmitter release, plasticity, and synaptic vesicle (SV) trafficking. Our work promises to gain deep understanding of synapses and to develop novel treatments for brain diseases. We use the calyx of Held in the auditory brainstem circuit as a model of central synapses.
Insulin Granule Trafficking and Diabetes
Dense core vesicles (DCVs) control the release of hormones that are essential for diverse cell signaling and function. To study DCV trafficking, we use pancreatic beta cells, which are the sole source of insulin production in mammals; dysfunction of beta cells is a hallmark of diabetes. Our recent work discovers an endocytosis-dependent regulation of insulin secretion in beta cells, highlighting a potential link between beta cell endocytosis and diabetes.
Nano-machinery of Vesicle Trafficking
How exocytosis and endocytosis are coupled at nerve terminals? This question remains unclear despite decades of research on each process. Nearly all genes and molecules in exocytosis and endocytosis have been identified and characterized, however, we know very little about how these two fundamental events are coupled in time and space under physiological condition. Moreover, a clear picture of the molecular architecture of release sites (SNARE, docking/priming factors, Ca2+ sensors, and Ca2+ channels) at synaptic active zones is also missing. We are developing innovative tools, including single-molecule localization super-resolution microscopy (SMLM), to understand the structure, dynamics, and regulation of these nano-machines in central synapses.
We are recruiting:
Postdoctoral fellows: Applicants who have experience with patch-clamp, optical nanoscopy (TIRF/PALM/STORM/STED), or molecular biology are especially welcome to apply. Please send a succinct research plan (one page) and your CV to email@example.com.
Graduate and undergraduate students
Dynamin deficiency causes insulin secretion failure and hyperglycemia.
(Fan F, Wu Y, Hara M, Rizk A, Ji C, Nerad D, Tamarina N, Lou X.) Proc Natl Acad Sci U S A. 2021 Aug 10;118(32) PMID: 34362840 PMCID: PMC8364113 SCOPUS ID: 2-s2.0-85112629945 08/08/2021
Imaging the Nanoscale Distribution of Phosphoinositides in the Cell Plasma Membrane with Single-Molecule Localization Super-Resolution Microscopy.
(Fan F, Ji C, Lou X.) Methods Mol Biol. 2021;2251:91-104 PMID: 33481233 SCOPUS ID: 2-s2.0-85100326544 01/23/2021
Real-Time Endocytosis Measurements by Membrane Capacitance Recording at Central Nerve Terminals.
(Lou X.) Methods Mol Biol. 2018;1847:95-108 PMID: 30129012 SCOPUS ID: 2-s2.0-85052248659 08/22/2018
Sensing Exocytosis and Triggering Endocytosis at Synapses: Synaptic Vesicle Exocytosis-Endocytosis Coupling.
(Lou X.) Front Cell Neurosci. 2018;12:66 PMID: 29593500 PMCID: PMC5861208 03/30/2018
Using novel imaging approaches to study phosphoinositide signaling in vesicle trafficking
(Lou X.) Protein-Lipid Interactions: Perspectives, Techniques and Challenges. 1 January 2018:107-132 SCOPUS ID: 2-s2.0-85049016121 01/01/2018
Vesicle Docking Is a Key Target of Local PI(4,5)P2 Metabolism in the Secretory Pathway of INS-1 Cells.
(Ji C, Fan F, Lou X.) Cell Rep. 2017 Aug 08;20(6):1409-1421 PMID: 28793264 PMCID: PMC5613661 SCOPUS ID: 2-s2.0-85026870735 08/10/2017
Dynamin-1 deletion enhances post-tetanic potentiation and quantal size after tetanic stimulation at the calyx of Held.
(Mahapatra S, Lou X.) J Physiol. 2017 Jan 01;595(1):193-206 PMID: 27229184 PMCID: PMC5199734 SCOPUS ID: 2-s2.0-84977537713 05/28/2016
Single-molecule Super-resolution Imaging of Phosphatidylinositol 4,5-bisphosphate in the Plasma Membrane with Novel Fluorescent Probes.
(Ji C, Lou X.) J Vis Exp. 2016 Oct 15(116) PMID: 27805608 PMCID: PMC5092206 SCOPUS ID: 2-s2.0-84992505061 11/03/2016
Dynamin 1- and 3-Mediated Endocytosis Is Essential for the Development of a Large Central Synapse In Vivo.
(Fan F, Funk L, Lou X.) J Neurosci. 2016 Jun 01;36(22):6097-115 PMID: 27251629 PMCID: PMC4887570 SCOPUS ID: 2-s2.0-84971673132 06/03/2016
Tissue-specific dynamin-1 deletion at the calyx of Held decreases short-term depression through a mechanism distinct from vesicle resupply.
(Mahapatra S, Fan F, Lou X.) Proc Natl Acad Sci U S A. 2016 May 31;113(22):E3150-8 PMID: 27185948 PMCID: PMC4896691 SCOPUS ID: 2-s2.0-84971572911 05/18/2016
Nanoscale Landscape of Phosphoinositides Revealed by Specific Pleckstrin Homology (PH) Domains Using Single-molecule Superresolution Imaging in the Plasma Membrane.
(Ji C, Zhang Y, Xu P, Xu T, Lou X.) J Biol Chem. 2015 Nov 06;290(45):26978-26993 PMID: 26396197 PMCID: PMC4646391 SCOPUS ID: 2-s2.0-84946780726 09/24/2015
Dynamin 2 regulates biphasic insulin secretion and plasma glucose homeostasis.
(Fan F, Ji C, Wu Y, Ferguson SM, Tamarina N, Philipson LH, Lou X.) J Clin Invest. 2015 Nov 02;125(11):4026-41 PMID: 26413867 PMCID: PMC4639984 SCOPUS ID: 2-s2.0-84946760942 09/29/2015