Pom1 is a polarity protein
kinase
In biochemistry, a kinase () is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the high-energy ATP molecule don ...
in fission yeast, ''
Schizosaccharomyces pombe
''Schizosaccharomyces pombe'', also called "fission yeast", is a species of yeast used in traditional brewing and as a model organism in molecular and cell biology. It is a unicellular eukaryote, whose cells are rod-shaped. Cells typically meas ...
'' (''S. pombe''), that localizes to cell ends and regulates cell division. As the cell lengthens, the level of Pom1 in the middle declines, which triggers mitosis.
[Bahler, J., and Pringle, J.R. “Pom1p, a fission yeast protein kinase that provides positional information for both polarized growth and cytokinesis.” Genes and Development 12, 1356-1370 (1998).]
The
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
br>
''pom1''codes for a protein 1087 amino acids long with the protein
kinase
In biochemistry, a kinase () is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the high-energy ATP molecule don ...
domain likely located at the carboxyl terminus.
Pom1 regulates a signaling pathway that includes
Cdk1
Cyclin-dependent kinase 1 also known as CDK1 or cell division cycle protein 2 homolog is a highly conserved protein that functions as a serine/threonine protein kinase, and is a key player in cell cycle regulation. It has been highly studied in th ...
and ultimately regulates
mitotic entry.
[Moseley, J.B., Mayeux, A., Paoletti, A. and Nurse, P. “A spatial gradient coordinates cell size and mitotic entry in fission yeast.” Nature 459, 857-861 (2009).] Cells with mutant pom1 form a septa and growth zone, but show a host of abnormalities including misplaced or misoriented septa, bi-polar growth replaced with random growth at one end, or the mislocalization of the growth axis leading to abnormal branching.
[Bahler, J., and Nurse, P. “Fission yeast Pom1p kinase activity is cell cycle regulated and essential for cellular symmetry during growth and division.” The EMBO Journal 20, 1064-1073 (2001).]
Pom1 plays an important role in differentiating the old and new end of an
S. pombe
''Schizosaccharomyces pombe'', also called "fission yeast", is a species of yeast used in traditional brewing and as a model organism in molecular and cell biology. It is a unicellular eukaryote, whose cells are rod-shaped. Cells typically meas ...
cell. Normal cell growth begins immediately in the old end of the cell and is delayed in the new end.
''pom1'' mutants show immediate growth at both ends. Since Pom1 has been shown to be highly concentrated at the new end and nearly absent from the old end, it, along with other factors are part of an inhibitory signal that prevents immediate growth from the new end.
Overexpression of Pom1 can also lead to the formation of new growth ends.
Pom1 is a relatively unique protein
kinase
In biochemistry, a kinase () is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the high-energy ATP molecule don ...
as its closest homolog in
S. pombe
''Schizosaccharomyces pombe'', also called "fission yeast", is a species of yeast used in traditional brewing and as a model organism in molecular and cell biology. It is a unicellular eukaryote, whose cells are rod-shaped. Cells typically meas ...
is only 55% identical. Homologs in other organisms include Dyrk in rats, Dyrk2 and Dyrk3 in humans, Yak1p in
S. cerevisiae
''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have bee ...
, and Minibrain in Drosophila and humans.
Cell localization
During
interphase
Interphase is the portion of the cell cycle that is not accompanied by visible changes under the microscope, and includes the G1, S and G2 phases. During interphase, the cell grows (G1), replicates its DNA (S) and prepares for mitosis (G2). A c ...
, Pom1 resides throughout the cell including the medial cortical nodes. Pom1’s localization to the poles during cell division is regulated by Tea1 and Tea2.
[Behrens, R., and Nurse, P. “Roles of fission yeast tea1p in the localization of polarity factors and in organizing the microtubular cytoskeleton.” The Journal of Cell Biology 157, 783-793 (2002).] In the absence of Tea1 and Tea2, Pom1 maintains its
kinase
In biochemistry, a kinase () is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the high-energy ATP molecule don ...
activity, but does not localize to the cell ends.
Microtubules
Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm and have an inner diameter between 11 an ...
also help localize Pom1 in the cell as Pom1 delocalization has been shown to result from
microtubule
Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm and have an inner diameter between 11 an ...
disassembly.
Structurally, both the catalytic and non-catalytic regions of Pom1 are necessary for cell end localization.
The Cdr2, Cdr1,
Wee1
Wee1 is a nuclear kinase belonging to the Ser/Thr family of protein kinases in the fission yeast ''Schizosaccharomyces pombe'' (''S. pombe'')Wee1has a molecular mass of 96 kDa and is a key regulator of cell cycle progression.
It influences ...
, Mid1, and Blt1 proteins are also located at the medial node during
interphase
Interphase is the portion of the cell cycle that is not accompanied by visible changes under the microscope, and includes the G1, S and G2 phases. During interphase, the cell grows (G1), replicates its DNA (S) and prepares for mitosis (G2). A c ...
and are believed to be part of the signaling pathway for mitotic entry.
[Morrell, J.L., Nichols, C.B., and Gould, K.L. “The GIN4 family kinase, Cdr2p, acts independently of septins in fission yeast. The Journal of Cell Science 117, 5293-5302 (2004).] Cdr2 localization to the cell middle is regulated by the expression of Pom1 and other signals as pom1 mutants allow Cdr2 to diffuse from the medial node localization to one half of the cell.
Cell Size and Spatial Gradient
![Pom1 Model](https://upload.wikimedia.org/wikipedia/commons/7/78/Pom1_Model.jpg)
Pom1 forms a spatial gradient as cells elongate throughout
G2 phase
G2 phase, Gap 2 phase, or Growth 2 phase, is the third subphase of interphase in the cell cycle directly preceding mitosis. It follows the successful completion of S phase, during which the cell’s DNA is replicated. G2 phase ends with the o ...
.
Figure 1 illustrates in cartoon form the gradient of Pom1 (shown by the dark shading) across first a relatively small cell during
interphase
Interphase is the portion of the cell cycle that is not accompanied by visible changes under the microscope, and includes the G1, S and G2 phases. During interphase, the cell grows (G1), replicates its DNA (S) and prepares for mitosis (G2). A c ...
and an elongated cell passing through
G2 phase
G2 phase, Gap 2 phase, or Growth 2 phase, is the third subphase of interphase in the cell cycle directly preceding mitosis. It follows the successful completion of S phase, during which the cell’s DNA is replicated. G2 phase ends with the o ...
. As cells elongate, Pom1 concentration peaks at the two poles and diminishes toward the center of the cell. Cdr2 reads the diminishing inhibitory signal from Pom1’s concentration gradient and activates Cdr1 and Blt1 that were localized at the medial node due to Cdr2 recruitment.
Cdr1 then phosphorylates and inhibits
Wee1
Wee1 is a nuclear kinase belonging to the Ser/Thr family of protein kinases in the fission yeast ''Schizosaccharomyces pombe'' (''S. pombe'')Wee1has a molecular mass of 96 kDa and is a key regulator of cell cycle progression.
It influences ...
, also recruited to the medial node by the presence of Cdr2.
The phosphorylated
Wee1
Wee1 is a nuclear kinase belonging to the Ser/Thr family of protein kinases in the fission yeast ''Schizosaccharomyces pombe'' (''S. pombe'')Wee1has a molecular mass of 96 kDa and is a key regulator of cell cycle progression.
It influences ...
allows
Cdc25
Cdc25 is a dual-specificity phosphatase first isolated from the yeast ''Schizosaccharomyces pombe'' as a cell cycle defective mutant. As with other cell cycle proteins or genes such as Cdc2 and Cdc4, the "cdc" in its name refers to "cell divisio ...
to dephosphorylate
Cdk1
Cyclin-dependent kinase 1 also known as CDK1 or cell division cycle protein 2 homolog is a highly conserved protein that functions as a serine/threonine protein kinase, and is a key player in cell cycle regulation. It has been highly studied in th ...
and move the cell into
mitosis
In cell biology, mitosis () is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is mainta ...
.
Figure 2 depicts a simplified signaling pathway for size-dependent mitotic entry based on this model. The inhibition of
Wee1
Wee1 is a nuclear kinase belonging to the Ser/Thr family of protein kinases in the fission yeast ''Schizosaccharomyces pombe'' (''S. pombe'')Wee1has a molecular mass of 96 kDa and is a key regulator of cell cycle progression.
It influences ...
directly by Cdr2 shown by the dashed line has yet to be confirmed.
Tests of the Pom1 Model
![Cell polarity](https://upload.wikimedia.org/wikipedia/commons/e/e6/Cell_polarity.jpg)
GFP-tagged Pom1 has been shown to create a gradient in elongated cells as characterized in Figure 1. According to Figure 2, the decreased Pom1 at the location of Cdr2 in the medial node decreases the inhibition of Cdr2. In confirmation of this model’s interaction, results show that cells with delocalized Pom1 that retain full
kinase
In biochemistry, a kinase () is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the high-energy ATP molecule don ...
activity from tea1 mutants delay mitotic entry. This is likely due to the continued inhibition of Cdr2.
Further experiments that ectopically localized Pom1 throughout the cortex also showed delayed mitotic entry equivalent to a ''cdr2'' knockdown suggesting once again that Pom1 inhibits Cdr2 and as Pom1 diminishes with cell elongation, Cdr2 begins a signaling pathway to inhibit
Wee1
Wee1 is a nuclear kinase belonging to the Ser/Thr family of protein kinases in the fission yeast ''Schizosaccharomyces pombe'' (''S. pombe'')Wee1has a molecular mass of 96 kDa and is a key regulator of cell cycle progression.
It influences ...
and eventually enter
mitosis
In cell biology, mitosis () is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is mainta ...
.
Future Research
It remains unclear if Cdr2 inhibits
Wee1
Wee1 is a nuclear kinase belonging to the Ser/Thr family of protein kinases in the fission yeast ''Schizosaccharomyces pombe'' (''S. pombe'')Wee1has a molecular mass of 96 kDa and is a key regulator of cell cycle progression.
It influences ...
directly or if it acts only indirectly through Cdr1 or other
kinases
In biochemistry, a kinase () is an enzyme that catalysis, catalyzes the transfer of phosphate groups from High-energy phosphate, high-energy, phosphate-donating molecules to specific Substrate (biochemistry), substrates. This process is known as ...
. Furthermore, Blt1, also localized at the medial node, may play a role in mitotic entry regulation. Blt1 mutants show increased length consistent with delayed mitotic entry.
Although currently unconfirmed, it is speculated that Blt1 acts by inhibiting
Wee1
Wee1 is a nuclear kinase belonging to the Ser/Thr family of protein kinases in the fission yeast ''Schizosaccharomyces pombe'' (''S. pombe'')Wee1has a molecular mass of 96 kDa and is a key regulator of cell cycle progression.
It influences ...
.
References
Mitosis