Abstract

Laminin is a heterotrimeric, extracellular matrix (ECM) protein that has been implicated in mediating various aspects of cell function and survival. We have recently found that laminin is highly expressed in the mouse hippocampus, and that proteolytic degradation of this protein can promote the death of neurons. In this application, we propose a systematic exploration of the expression and function of laminin in the central nervous system (CNS). Specifically, we will determine the isoform(s) of laminin that is expressed in the hippocampus, identify the proteases directly responsible for its degradation and their sites of cleavage, and establish which region of laminin interacts with neurons to promote survival. Armed with this information, we will produce conditional knockout mice that lack the specific CNS laminin isoforms only in the hippocampus. These experiments will define the molecular characteristics and functional role of a critical ECM component in the mammalian CNS.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
7R01NS038472-03
Application #
6330590
Study Section
Pathobiochemistry Study Section (PBC)
Program Officer
Leblanc, Gabrielle G
Project Start
1999-04-23
Project End
2003-03-31
Budget Start
2000-07-01
Budget End
2001-03-31
Support Year
3
Fiscal Year
2000
Total Cost
$342,474
Indirect Cost

  Institution

Name
Rockefeller University
Department
Biology
Type
Other Domestic Higher Education
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065

  Publications

McKee, Karen K; Yang, Dong-Hua; Patel, Rajesh et al. (2012) Schwann cell myelination requires integration of laminin activities. J Cell Sci 125:4609-19
Carlson, Karen B; Singh, Prabhjot; Feaster, Moses M et al. (2011) Mesenchymal stem cells facilitate axon sorting, myelination, and functional recovery in paralyzed mice deficient in Schwann cell-derived laminin. Glia 59:267-77
Yu, Wei-Ming; Yu, Huaxu; Chen, Zu-Lin et al. (2009) Disruption of laminin in the peripheral nervous system impedes nonmyelinating Schwann cell development and impairs nociceptive sensory function. Glia 57:850-9
Yu, Wei-Ming; Chen, Zu-Lin; North, Alison J et al. (2009) Laminin is required for Schwann cell morphogenesis. J Cell Sci 122:929-36
Skrzypiec, Anna E; Maiya, Rajani; Chen, Zulin et al. (2009) Plasmin-mediated degradation of laminin gamma-1 is critical for ethanol-induced neurodegeneration. Biol Psychiatry 66:785-94
Chen, Zu-Lin; Haegeli, Véronique; Yu, Huaxu et al. (2009) Cortical deficiency of laminin gamma1 impairs the AKT/GSK-3beta signaling pathway and leads to defects in neurite outgrowth and neuronal migration. Dev Biol 327:158-68
Dhadialla, Prabhjot S; Ohiorhenuan, Ifije E; Cohen, Andrew et al. (2009) Maximum-entropy network analysis reveals a role for tumor necrosis factor in peripheral nerve development and function. Proc Natl Acad Sci U S A 106:12494-9
Chernousov, Michael A; Yu, Wei-Ming; Chen, Zu-Lin et al. (2008) Regulation of Schwann cell function by the extracellular matrix. Glia 56:1498-507
Yu, Wei-Ming; Yu, Huaxu; Chen, Zu-Lin (2007) Laminins in peripheral nerve development and muscular dystrophy. Mol Neurobiol 35:288-97
Schaefer, Ulrich; Vorlova, Sandra; Machida, Takuji et al. (2007) Modulation of sympathetic activity by tissue plasminogen activator is independent of plasminogen and urokinase. J Pharmacol Exp Ther 322:265-73

Showing the most recent 10 out of 24 publications