Disease relevance of CHS3

• We have tagged Chs3p, the putative catalytic subunit of CSIII, with the immunoreactive epitope of influenza virus hemagglutinin to follow expression of the protein [1].

High impact information on CHS3

• In Saccharomyces cerevisiae, the synthesis of chitin is temporally and spatially regulated through the transport of Chs3p (chitin synthase III) to the plasma membrane in the bud neck region [2].
• Traffic of Chs3p from the trans-Golgi network (TGN)/early endosome to the plasma membrane requires the function of Chs5p and Chs6p [2].
• In the absence of CHS7 product, Chs3p, but not other secreted proteins, is retained in the ER, leading to a severe defect in CSIII activity and consequently, to a reduced rate of chitin synthesis [3].
• This localization depends on the septins but not on Chs4p or Chs3p [4].
• This localization is dependent on the septins, Bni4p, and Chs3p [4].

Biological context of CHS3

• Deletion of the CHS3 gene severely compromised the phenotype of gas1 cells, despite the fact that CSIII activity, assayed in membrane fractions, did not change [5].
• Chs4p does not act as a transcriptional or translational regulator of CHS3, the gene coding for the catalytic subunit of CSIII activity, and we therefore propose that Chs4p would be an essential component of the CSIII complex, acting as a post-translational regulator of this activity [6].
• Chitin septum biogenesis is catalyzed by two distinct chitin synthase activities encoded by the CHS2 and CHS3 genes [7].
• In addition to finding, not surprisingly, that mutations in major cell wall-related genes such as FKS1 (glucan synthase) and mutations in any of the Golgi glycosylation complex genes (MNN9 family) are lethal in combination with chs3Delta, we found that a mutation in Srv2p, a bifunctional regulatory gene, is notably lethal in the chs3 deletion [8].
• The three chitin synthases of Saccharomyces cerevisiae, Chs1, Chs2, and Chs3, participate in septum and cell wall formation of vegetative cells and in wall morphogenesis of conjugating cells and spores [9].

Anatomical context of CHS3

• The chitin level in the cell walls of a strain lacking both BGL2 and CHS3 genes was higher than that in chs3Delta and lower than that in bgl2Delta strains [10].
• Treatment of Chs3-containing membranes with detergents drastically reduced the enzymatic activity [11].
• The traffic of Chs3p to the cell surface from the trans-Golgi network (TGN) depends on two proteins, Chs5p and Chs6p, which sort selected cargo proteins into secretory vesicles [12].
• Chs6p-dependent anterograde transport of Chs3p from the chitosome to the plasma membrane in Saccharomyces cerevisiae [13].
• Collectively, these data suggest that the trafficking of Chs2p and Chs3p diverges after endocytosis; Chs3p is not delivered to the vacuole, but instead may be recycled [14].

Associations of CHS3 with chemical compounds

• BACKGROUND: In S. cerevisiae the beta-1,4-linked N-acetylglucosamine polymer, chitin, is synthesized by a family of 3 specialized but interacting chitin synthases encoded by CHS1, CHS2 and CHS3 [15].
• In Saccharomyces cerevisiae, the polysaccharide chitin is deposited at the mother bud junction by an integral membrane enzyme, chitin synthase 3 (Chs3p) [12].
• No increase in chitin synthase 3 (Chs3) activity in bgl2Delta cells was observed, while they became more sensitive to Nikkomycin Z [10].
• Alanine substitutions for the conserved amino acids in con2 identified five amino acids, Asn797, His799, Asp800, Trp803, and Thr805, the mutation of which severely diminished enzymatic activity and the enzyme's ability to rescue the yeast chs2 delta chs3 delta null mutant strain [16].
• Mutant dit101, however, was additionally lacking the chitosan layer of the spore wall [17].

Co-localisations of CHS3

• Sps1p colocalized with Chs3p to peripheral and internal punctate structures and prospore membranes [18].

Regulatory relationships of CHS3

• Consistent with this, overexpression of Chs4p under the regulation of the ScGAL1 promoter enhanced chitin synthase 3 activity in S. cerevisiae 7- to 38-fold [19].
• The phosphoinositide phosphatase Sac1p controls trafficking of the yeast Chs3p chitin synthase [20].
• Ypt32p regulates the translocation of Chs3p from an internal pool to the plasma membrane [21].
• We propose that Ypt31/32p have a role in regulating the delivery of Chs3p to the plasma membrane and deposition of chitin at the cell surface [21].
• Chs4p thus promotes Chs3p translocation into the plasma membrane in a stable and active form [22].

Other interactions of CHS3

• We screened Saccharomyces strains for mutants that are synthetically lethal with deletion of the major chitin synthase gene CHS3 [8].
• However, chs5 cells produce more chitin than chs3 mutants, indicating that CHS5 plays a role in other processes besides chitin synthesis [23].
• CHS3 expression was not affected in the gas1 mutant [5].
• However, the amount of DIT101 transcript changed significantly at different stages of the mitotic cell cycle, peaking after septum formation, but before cytokinesis [17].
• Finally, immunofluorescence experiments reveal that in small-budded cells, sbe2 sbe22 mutants mislocalize Chs3p, a protein involved in chitin synthesis [24].

Analytical, diagnostic and therapeutic context of CHS3

• Subcellular fractionation and indirect immunofluorescence indicate that Chs3p distribution is altered in chs6 mutant cells [13].
• The encoded chitin synthase product (WdChs4p) showed high homology with Chs3p of Saccharomyces cerevisiae and other class IV chitin synthases, and Northern blotting showed that WdCHS4 was expressed at constitutive levels under all conditions tested [25].
• Western blotting confirmed that Chs3p was extracted from membranes by CHAPS and cholesteryl hemisuccinate and revealed that Chs4p was also solubilized using these detergents [26].

References