Affiliation:
1. Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-8240
Abstract
ABSTRACT
The inositol 1,3,4,5,6-pentakisphosphate (IP
5
) 2-kinase (Ipk1) catalyzes the production of inositol hexakisphosphate (IP
6
) in eukaryotic cells. Previous studies have shown that IP
6
is required for efficient nuclear mRNA export in the budding yeast
Saccharomyces cerevisiae
. Here, we report the first functional analysis of
ipk1
+
in
Schizosaccharomyces pombe. S. pombe
Ipk1 (SpIpk1) is unique among Ipk1 orthologues in that it harbors a novel amino (N)-terminal domain with coiled-coil structural motifs similar to those of BAR (Bin-amphiphysin-Rvs) domain proteins. Mutants with
ipk1
+
deleted (
ipk1
Δ) had mRNA export defects as well as pleiotropic defects in polarized growth, cell morphology, endocytosis, and cell separation. The SpIpk1 catalytic carboxy-terminal domain was required to rescue these defects, and the mRNA export block was genetically linked to SpDbp5 function and, likely, IP
6
production. However, the overexpression of the N-terminal domain alone also inhibited these functions in wild-type cells. This revealed a distinct noncatalytic function for the N-terminal domain. To test for connections with other inositol polyphosphates, we also analyzed whether the loss of
asp1
+
function, encoding an IP
6
kinase downstream of Ipk1, had an effect on
ipk1
Δ cells. The
asp1
Δ mutant alone did not block mRNA export, and its cell morphology, polarized growth, and endocytosis defects were less severe than those of
ipk1
Δ cells. Moreover,
ipk1
Δ
asp1
Δ double mutants had altered inositol polyphosphate levels distinct from those of the
ipk1
Δ mutant. This suggested novel roles for
asp1
+
upstream of
ipk1
+
. We propose that IP
6
production is a key signaling linchpin for regulating multiple essential cellular processes.
Publisher
American Society for Microbiology
Subject
Molecular Biology,General Medicine,Microbiology
Cited by
11 articles.
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