Disease relevance of SPA2

• The SPA2 gene was fused to the Escherichia coli trpE gene, and polyclonal antibodies were prepared to the fusion protein [1].

High impact information on SPA2

• Spa2p and Cdc10p both participate in bud site selection and cell morphogenesis in yeast, and spa2delta cdc10-10 cells are inviable [2].
• After pheromone treatment, Bni1p-GFP and Spa2p failed to localize to the cortex of fus3 mutants, and cell wall growth became completely unpolarized [3].
• Cdc42p and Spa2p, two proteins that normally also move to the bud site in a process independent from actin organization, failed to localize properly in rho1(E45I) [4].
• SPH1, which is similar to SPA2, is required for bipolar budding and plays a role in shmoo formation [5].
• Finally, during cytokinesis Spa2p is present as a ring at the mother-daughter bud neck [5].

Biological context of SPA2

• We previously identified mutants defective in PEA2 and SPA2 which alter cell polarization in the presence of mating pheromone in a similar manner (Chenevert, J., N. Valtz, and I. Herskowitz. 1994. Genetics, 136:1287-1297) [6].
• The Saccharomyces cerevisiae SPA2 protein localizes at sites involved in polarized cell growth in budding cells and mating cells. spa2 mutants have defects in projection formation during mating but are healthy during vegetative growth [7].
• Searching the yeast genome database revealed a previously uncharacterized protein which we name, Sph1p (a2p omolog), with significant homology to the localization domain and amino terminus of Spa2p [5].
• The yeast protein Spa2p localizes to growth sites and is important for polarized morphogenesis during budding, mating, and pseudohyphal growth [8].
• Spa2p interacts with cell polarity proteins and signaling components involved in yeast cell morphogenesis [8].

Anatomical context of SPA2

• Analysis of Fus- zygotes indicated that Fus1p was required for the normal localization of the vesicles to the zone of cell fusion, and Spa2p facilitated their clustering [9].
• By middle G1, most cells contain the SPB on the side of the nucleus proximal to the SPA2 patch, and a long extranuclear microtubule bundle intersects this patch [10].

Physical interactions of SPA2

• One of the regions involved in Spa2p stability and localization interacts with Pea2p; this region contains a conserved domain, SHD-II [8].
• Shs1p: a novel member of septin that interacts with spa2p, involved in polarized growth in saccharomyces cerevisiae [11].

Regulatory relationships of SPA2

• Therefore, we suggest that Mid1 function is influenced by Spa2 function through polarized morphogenesis [12].

Other interactions of SPA2

• These results suggest that Pea2p and Spa2p function together as a complex to generate the bipolar budding pattern and to guarantee proper polarization during mating [6].
• By using the two-hybrid system, Spa2p and Bud6p were also found to interact with components of two mitogen-activated protein kinase (MAPK) pathways important for polarized cell growth [8].
• In addition, we found that the defect in default mating caused by mutations in SPA2 is partially suppressed by multiple copies of two genes, FUS2 and MFA2 [13].
• However, in the spa2 mutant, Bni1p was not localized at the bud tip and instead localized diffusely in the cytoplasm [14].
• SSF1 overexpression preferentially increased the mating efficiency of a strain containing a null allele of SPA2, a gene that functions specifically in cell morphology [15].

Analytical, diagnostic and therapeutic context of SPA2

• Immunofluorescence experiments indicate that the SPA2 gene product has a sharply polarized distribution in yeast cells [1].
• In addition, we observe an enhanced cell-separation defect in a myo1spa2 strain at 37 degrees C. This provides further evidence that Spa2p is involved in cytokinesis and cell wall morphogenesis [16].

References