Lines of investigation
Tissue-level organization of cells in animals is supported by the basement membrane (BM), a planar polymer of extracellular matrix proteins that underlies epithelia and surrounds organs and nervous tissue. Understanding tissue architecture and its underlying cellular and molecular determinants is essential for deciphering the mechanisms of normal nervous system morphogenesis and altered physiology in disease and aging. In our laboratory, we use the fruit fly Drosophila melanogaster to study the secretion and assembly of the BM. Taking advantage of the sophisticated genetic tools available in Drosophila, and in combination with advanced imaging, we are investigating the biogenesis of BM components, their assembly into normal and fibrotic polymers, and their roles in the morphogenesis of the nervous system, intercellular signaling, immune responses, regeneration and tumor progression.
A particularly interesting aspect of the biogenesis of the extracellular matrix is its trafficking through the secretory pathway. The huge dimensions of collagen and other matrix proteins make them prone to age-dependent aggregation and challenge our current models of how secretion works. In this regard, we are examining the highly specialized organization of the secretory pathway in neurons and their so-called “Golgi ouposts”: Golgi fragments lacking the polarized organization typical of this organelle. Understanding outpost formation may shed light on the causes and consequences of Golgi fragmentation, notably increased in neurodegenerative diseases.
- ER exit sites in Drosophila display abundant ER-Golgi vesicles and pearled tubes but no megacarriers Yang K, Liu M, Feng Z, Rojas M, Zhou L, Ke H, Pastor-Pareja JC Cell Rep. 2021 36:109707 https://doi.org/10.1016/j.celrep.2021.109707
- Atypical laminin spots and pull-generated microtubule-actin projections mediate Drosophila wing adhesion Sun T, Song Y, Teng D, Chen Y, Dai J, Ma M, Zhang W, Pastor-Pareja JC Cell Rep. 2021 36:109667 https://doi.org/10.1016/j.celrep.2021.109667
- Spectraplakin Shot maintains perinuclear microtubule organization in Drosophila polyploid cells Sun T, Song Y, Dai J, Mao D, Ma M, Ni J-Q, Liang X, Pastor-Pareja JC Dev Cell 2019 49:731-747.e7 https://doi.org/10.1016/j.devcel.2019.03.027
- Tango1 spatially organizes ER exit sites to control ER export Liu M, Feng Z, Ke H, Liu Y, Sun T, Dai J, Cui W, Pastor-Pareja JC J Cell Biol 2017 216:1035-1059 https://doi.org/10.1083/jcb.201611088
- Basement membrane manipulation in Drosophila wing discs affects Dpp retention but not growth mechanoregulation Ma M, Cao, Dai J, Pastor-Pareja JC Dev Cell 2017 42:97-106.e4 https://doi.org/10.1016/j.devcel.2017.06.004