Publications by authors named "Leigh C Coates"

Neuroserpin is an inhibitor of tissue plasminogen activator (tPA) that is expressed in developing and adult nervous systems. Spatial and temporal analysis of neuroserpin expression suggests that it is involved in regulating the proteolytic balance associated with axonogenesis and synaptogenesis during development and synaptic plasticity in the adult. Here we demonstrate that altered expression of neuroserpin modulates the degree of cell-cell adhesion in pheochromocytoma PC12 cells independently of its role as an inhibitor of tPA.

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Myeloid progenitors in the bone marrow differentiate into most of the major cell types of the immune system, including macrophages and dendritic cells. These cells play important roles in both innate and adaptive immunity. They express a number of proteases and protease inhibitors including members of the serine proteinase inhibitor or serpin superfamily.

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The biosynthesis of hormones and neuropeptides involves post-translational cleavage of precursors at basic amino acids by prohormone convertases (PCs) predominantly in secretory granules that bud from the trans-Golgi Network. This study reports that the amino acid sequence of PC3 (aa617-638), previously identified as a novel transmembrane (TM) domain, confers lipid raft association and facilitates sorting of the enzyme to the secretory granules of Neuro2A cells for prohormone cleavage. Floatation analysis on sucrose density gradients showed that a proportion of full length (PC3-FL) and carboxyl terminus-truncated PC3(1-638) (PC3-638) containing the TM domain were associated with lipid rafts in Neuro2A cells, while PC3(1-616) (PC3-616) and PC3-DeltaTM lacking the TM domain were not.

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Article Synopsis
  • The biosynthesis of biologically active peptides relies on prohormone convertases like PC3, which process precursor proteins through limited proteolysis in secretory granules.
  • PC3 shows a specific interaction with secretory granule membranes and is associated with lipid rafts, as evidenced by resistance to extraction techniques and behavior in sucrose gradients.
  • A novel form of PC3, designated 64 kDa PC3-TM, has been identified with a transmembrane domain, indicating a potential model where PC3 is anchored to lipid rafts, facilitating the targeting of other proteins to secretory granules.
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Serine proteases play essential roles in a wide variety of cellular processes in endocrine cells. There is a growing interest in the roles of serine protease inhibitors, or serpins, as key regulators of their activity. We have cloned two neuroserpin cDNAs from a rat pituitary cDNA library and confirmed tissue plasminogen activator as a potential target for this inhibitor.

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Neuroserpin is a serine protease inhibitor widely expressed in the developing and adult nervous systems and implicated in the regulation of proteases involved in processes such as synaptic plasticity, neuronal migration and axogenesis. We have analysed the effect of neuroserpin on growth factor-induced neurite outgrowth in PC12 cells. We show that small changes in neuroserpin expression result in changes to the number of cells extending neurites and total neurite length following NGF treatment.

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