Yeast Irc6p is a novel type of conserved clathrin coat accessory factor related to small G proteins.

Clathrin coat accessory proteins play key roles in transport mediated by clathrin-coated vesicles. Yeast Irc6p and the related mammalian p34 are putative clathrin accessory proteins that interact with clathrin adaptor complexes. We present evidence that Irc6p functions in clathrin-mediated traffic between the trans-Golgi network and endosomes, linking clathrin adaptor complex AP-1 and the Rab GTPase Ypt31p. The crystal structure of the Irc6p N-terminal domain revealed a G-protein fold most related to small G proteins of the Rab and Arf families. However, Irc6p lacks G-protein signature motifs and high-affinity GTP binding. Also, mutant Irc6p lacking candidate GTP-binding residues retained function. Mammalian p34 rescued growth defects in irc6 cells, indicating functional conservation, and modeling predicted a similar N-terminal fold in p34. Irc6p and p34 also contain functionally conserved C-terminal regions. Irc6p/p34-related proteins with the same two-part architecture are encoded in genomes of species as diverse as plants and humans. Together these results define Irc6p/p34 as a novel type of conserved clathrin accessory protein and founding members of a new G protein-like family

Clathrin Adaptor Complex-interacting Protein Irc6 Functions through the Conserved C-Terminal Domain.

Clathrin coats drive transport vesicle formation from the plasma membrane and in pathways between the trans-Golgi network (TGN) and endosomes. Clathrin adaptors play central roles orchestrating assembly of clathrin coats. The yeast clathrin adaptor-interacting protein Irc6 is an orthologue of human p34, which is mutated in the inherited skin disorder punctate palmoplantar keratoderma type I. Irc6 and p34 bind to clathrin adaptor complexes AP-1 and AP-2 and are members of a conserved family characterized by a two-domain architecture. Irc6 is required for AP-1-dependent transport between the TGN and endosomes in yeast. Here we present evidence that the C-terminal two amino acids of Irc6 are required for AP-1 binding and transport function. Additionally, like the C-terminal domain, the N-terminal domain when overexpressed partially restores AP-1-mediated transport in cells lacking full-length Irc6. These findings support a functional role for Irc6 binding to AP-1. Negative genetic interactions with irc6∆ are enriched for genes related to membrane traffic and nuclear processes, consistent with diverse cellular roles for Irc6

Spatial dimensions of biodiversity values: analyses of preference heterogeneity and conservation priorities across national landscapes

This thesis contributes to our understanding of the spatial dimension of biodiversity related values in the context of changing environment. It starts with making a case for the use economic valuation for improving decision making related to environmental change and with an overview of the main concepts and approaches for doing so (Chapter 1). The thesis highlights the need to better incorporate the spatial considerations in ecosystem assessments and the importance of robust natural science that underpins any such assessments. The thesis then provides three empirical analyses, two that employ discrete choice modelling to examine how spatial information influences preferences for environmental change, and one that focuses on modelling the biodiversity impacts of land use change. The contributions of the thesis are as follows. 1) development of a novel methodology for choice experiments that incorporates space in the survey design, experimental design and presentation of choice situations on individualised maps (Chapter 3); 2) application of this methodology to test how addition of individualised maps alongside commonly used Tabular format impacts on preferences and welfare values for environmental change (Chapter 3); 3) provision of evidence that state and country borders have an impact on preferences for the portrayed changes (Chapter 2 and 3); and 4) development of prediction models that allow evaluating land use change impacts on farmland bird species; this includes assessment of model performance and variables importance for future integration of the models with economic analyses (Chapter 4). The thesis closes with research implications and personal research plans