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Jem A. Efe, Scott D. Emr. Division of Biology & HHMI,
UC San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0668, USA.
MON2 was first identified in a genetic screen for mutants that
exhibit synthetic lethality with deletion of YPT51. Accordingly, a
strain lacking MON2 exhibits defects in protein sorting and vacuole
biogenesis, as well as impaired growth and endocytosis
(Singer-Krueger and Ferro-Novick 1997). Furthermore, Mon2p-GFP
localizes to punctate structures in the cytosol and is peripherally
associated with light membranes (Jochum, Jackson et al. 2002). Our
studies have shown that mon2delta cells, in addition to a delay in
ALP processing, exhibit a partial block in APeI maturation via the
constitutive Cvt pathway. This defect resembles that of the GARP
complex (VPS51-54) mutants as well as ypt6delta. Electron microscopy
of the mon2delta strain has revealed an accumulation of membranous
inclusions in the cytoplasm. These findings suggest a role for Mon2p
at the late Golgi/early endosomes, an observation supported by
colocalization of Mon2-GFP with Sec7-DsRed and DsRed-PH chimeras. We
have found that deletion of MON2 is synthetically lethal with a set
of genes critical for retrograde traffic to the late Golgi.
Moreover, proteins known to recycle through the Golgi are
mislocalized in the mon2delta strain at high temperature. Based on
structure-function studies, we have concluded that the N terminus of
the protein mediates its localization, while the C terminus harbors
a critical functional domain. Our recent findings on the
localization and activity of Mon2p will be presented.
Program Nr. 227B from 2004 Yeast meeting |
