Abstract

The broad objective of the proposed research is to determine the natural history of lysosomal enzymes in normal cells from patients with genetic diseases. This research is designed to deduce the mechanisms by which cells selectively internalize hydrolytic enzymes and package them into lysosomes. The cell surface receptors for lysosomal hydrolases will be purified and characterized. Anti-receptor antibodies will be raised and used to follow the endocytosis of receptor and define the mechanisms of receptor recycling. Lysosomal organelles, residual bodies and GERL, will be isolated from cultured human fibroblasts. Lysosomal membrane will be analyzed for lipid and protein content and compared to membranes of cells from patients with lysosomal abnormalities. Lysosome fusion will be examined in vitro to detect membrane and enzyme exchange. Model systems will be developed with purified lysosomes and artificial vesicles called liposomes, to establish the chemical requirements that control organelle fusion.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program Projects (P01)
Project #
5P01HD006576-13
Application #
3096586
Study Section
Mental Retardation Research and Training Committee (HDMR)
Project Start
1983-09-30
Project End
1986-08-31
Budget Start
1985-09-01
Budget End
1986-08-31
Support Year
13
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of California Los Angeles
Department
Type
Hospitals
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095

  Publications

Krityakiarana, Warin; Zhao, Paul M; Nguyen, Kevin et al. (2016) Proof-of Concept that an Acute Trophic Factors Intervention After Spinal Cord Injury Provides an Adequate Niche for Neuroprotection, Recruitment of Nestin-Expressing Progenitors and Regeneration. Neurochem Res 41:431-49
Espinosa-Jeffrey, Araceli; Blanchi, Bruno; Biancotti, Juan Carlos et al. (2016) Efficient Generation of Viral and Integration-Free Human Induced Pluripotent Stem Cell-Derived Oligodendrocytes. Curr Protoc Stem Cell Biol 38:2D.18.1-2D.18.27
Abad, Catalina; Cheung-Lau, Gardenia; Coûté-Monvoisin, Anne-Claire et al. (2015) Vasoactive intestinal peptide-deficient mice exhibit reduced pathology in trinitrobenzene sulfonic acid-induced colitis. Neuroimmunomodulation 22:203-12
Tsoa, Rosemarie W; Coskun, Volkan; Ho, Chi K et al. (2014) Spatiotemporally different origins of NG2 progenitors produce cortical interneurons versus glia in the mammalian forebrain. Proc Natl Acad Sci U S A 111:7444-9
Espinosa-Jeffrey, Araceli; Barajas, Socorro A R; Arrazola, Alfonso R et al. (2013) White matter loss in a mouse model of periventricular leukomalacia is rescued by trophic factors. Brain Sci 3:1461-82
Xue, Zhigang; Huang, Kevin; Cai, Chaochao et al. (2013) Genetic programs in human and mouse early embryos revealed by single-cell RNA sequencing. Nature 500:593-7
Yan, Yan; Zhou, Xiaofeng; Pan, Zui et al. (2013) Pro- and anti-mitogenic actions of pituitary adenylate cyclase-activating polypeptide in developing cerebral cortex: potential mediation by developmental switch of PAC1 receptor mRNA isoforms. J Neurosci 33:3865-78
de Vellis, Jean; Cole, Ruth (2012) Preparation of mixed glial cultures from postnatal rat brain. Methods Mol Biol 814:49-59
Ghiani, Cristina A; Mattan, Natalia S; Nobuta, Hiroko et al. (2011) Early effects of lipopolysaccharide-induced inflammation on foetal brain development in rat. ASN Neuro 3:
Hirose, Megumi; Niewiadomski, Pawel; Tse, Gary et al. (2011) Pituitary adenylyl cyclase-activating peptide counteracts hedgehog-dependent motor neuron production in mouse embryonic stem cell cultures. J Neurosci Res 89:1363-74

Showing the most recent 10 out of 151 publications