Peter Yurchenco Professor UMDNJ-RWJMS Dept. of Pathology Piscataway. NJ 08854 (732) 235-4674 FAX - 4825 yurchenc@umdnj.edu Visit the Yurchenco Lab!

Assembly. structure and function of basement membranes

Basement membranes are specialized cell-associated extracellular matrices whose molecular architectures are created through specific binding interactions of unique monomers. These matrices have support. perm-selective and cell regulatory functions. Both structure and function are altered in a number of diseases such as diabetes mellitus. Alports Syndrome. epidermolysis bullosa and some forms of congenital muscular dystrophy. The monomeric untis of basement membranes are. in themselves. large multi-domain glycoproteins and proteoglycans. each with several functions. Laminin and type IV collagen. for example. form polymeric networks as well as selectively bind and activate a number of different cellular receptors. Our fundamental research goals are to understand structure/function relationships in basement membranes at a molecular level of resolution. in particular: (a) the mechanisms of self-assembly and its regulation. the resulting molecular architectures. and how supramolecular organization contributes to function. (b) how structure and function become altered in diabetes. (c) the ole. and structural basis. of basement membranes. and their supramolecular assemblies. in the transmission of information to cells. These signals are mediated by beta-1. beta-3. and beta-4 class integrins. dystroglycan. and other cell-surface proteoglycans. and (d) the differential structural and cell-interactive information carried by the genetic variants of laminin and type IV collagen.

Selected Publications

Yurchenco PD, Patton BL. (2009) Developmental and pathogenic mechanisms of basement membrane assembly. Curr Pharm Des. 15(12):1277-94.

McKee KK, Capizzi S, Yurchenco PD. (2009) Scaffold-forming and adhesive contributions of synthetic laminin-binding proteins to basement membrane assembly. J Biol Chem. 284(13):8984-94.

Wu X, Li S, Chrostek-Grashoff A, Czuchra A, Meyer H, Yurchenco PD, Brakebusch C. (2007) Cdc42 is crucial for the establishment of epithelial polarity during early mammalian development. Dev Dyn. 236(10):2767-78.

McKee KK, Harrison D, Capizzi S, Yurchenco PD. (2007) Role of laminin terminal globular domains in basement membrane assembly. J Biol Chem. 282(29):21437-47.

Myers JC, Amenta PS, Dion AS, Sciancalepore JP, Nagaswami C, Weisel JW, Yurchenco PD. (2007) The molecular structure of human tissue type XV presents a unique conformation among the collagens. Biochem J. 404(3):535-44.

Colognato H, Galvin J, Wang Z, Relucio J, Nguyen T, Harrison D, Yurchenco PD, Ffrench-Constant C. (2007) Identification of dystroglycan as a second laminin receptor in oligodendrocytes, with a role in myelination. Development. 134(9):1723-36.

Harrison D, Hussain SA, Combs AC, Ervasti JM, Yurchenco PD, Hohenester E. (2007) Crystal structure and cell surface anchorage sites of laminin alpha1LG4-5. J Biol Chem. 282(15):11573-81.

Li S, Yurchenco PD. (2006) Matrix assembly, cell polarization, and cell survival: analysis of peri-implantation development with cultured embryonic stem cells. Methods Mol Biol. 329:113-25.

Smirnov SP. Barzaghi P. McKee KK. Ruegg MA. Yurchenco PD. (2005) Conjugation of LG domains of agrins and perlecan to polymerizing laminin-2 promotes acetylcholine receptor clustering. J Biol Chem. 280(50):41449-57.

Aumailley M. Bruckner-Tuderman L. Carter WG. Deutzmann R. Edgar D. Ekblom P. Engel J. Engvall E. Hohenester E. Jones JC. Kleinman HK. Marinkovich MP. Martin GR. Mayer U. Meneguzzi G. Miner JH. Miyazaki K. Patarroyo M. Paulsson M. Quaranta V. Sanes JR. Sasaki T. Sekiguchi K. Sorokin LM. Talts JF. Tryggvason K. Uitto J. Virtanen I. von der Mark K. Wewer UM. Yamada Y. Yurchenco PD. (2005) A simplified laminin nomenclature. Matrix Biol. 24(5):326-32.

Li S. Bordoy R. Stanchi F. Moser M. Braun A. Kudlacek O. Wewer UM. Yurchenco PD. Fassler R. (2005) PINCH1 regulates cell-matrix and cell-cell adhesions. cell polarity and cell survival during the peri-implantation stage. J Cell Sci. 118(Pt 13):2913-21.

Li S. Liquari P. McKee KK. Harrison D. Patel R. Lee S. Yurchenco PD. (2005) Laminin-sulfatide binding initiates basement membrane assembly and enables receptor signaling in Schwann cells and fibroblasts. J Cell Biol. 169(1):179-89.

Miner JH. Yurchenco PD. (2004) Laminin functions in tissue morphogenesis. Annu Rev Cell Dev Biol. 20:255-84.

Yurchenco PD. Wadsworth WG. (2004) Assembly and tissue functions of early embryonic laminins and netrins. Curr Opin Cell Biol. 16(5):572-9.

Yurchenco PD. Amenta PS. Patton BL. (2004) Basement membrane assembly. stability and activities observed through a developmental lens. Matrix Biol. 22(7):521-38.

Yurchenco PD. Cheng YS. Campbell K. Li S. (2004) Loss of basement membrane. receptor and cytoskeletal lattices in a laminin-deficient muscular dystrophy. J Cell Sci. 117(Pt 5):735-42.

Calzada MJ. Sipes JM. Krutzsch HC. Yurchenco PD. Annis DS. Mosher DF. Roberts DD. (2003) Recognition of the N-terminal modules of thrombospondin-1 and thrombospondin-2 by alpha6beta1 integrin. J Biol Chem. 278(42):40679-87.

Huang CC. Hall DH. Hedgecock EM. Kao G. Karantza V. Vogel BE. Hutter H. Chisholm AD. Yurchenco PD. Wadsworth WG.(2003) Laminin alpha subunits and their role in C. elegans development. Development. 130(14):3343-58.

Li S. Edgar D. Fassler R. Wadsworth W. Yurchenco PD. (2003) The role of laminin in embryonic cell polarization and tissue organization. Developmental Cell. 4(5):613-24.

Sakai T. Li S. Docheva D. Grashoff C. Sakai K. Kostka G. Braun A. Pfeifer A. Yurchenco PD. Fassler R. (2003) Integrin-linked kinase (ILK) is required for polarizing the epiblast. cell adhesion. and controlling actin accumulation. Genes & Development. 17(7):926-40.

Yurchenco PD. Smirnov S. Mathus T. (2002) Analysis of basement membrane self-assembly and cellular interactions with native and recombinant glycoproteins. Methods in Cell Biology. 69:111-44

Rybakova IN. Patel JR. Davies KE. Yurchenco PD. Ervasti JM. (2002) Utrophin binds laterally along actin filaments and can couple costameric actin with sarcolemma when overexpressed in dystrophin-deficient muscle. Molecular Biology of the Cell. 13(5):1512-21.