Psychiatry related information on TPM1

• We find that selective destabilization of actin cables in a strain lacking the tropomyosin 1 gene (TPM1) has no significant effect on the velocity of mitochondrial motor activity in vivo or in vitro [1].

High impact information on TPM1

• Disruption of TPM1 is not lethal, but results in a reduced growth rate and disappearance of actin cables [2].
• The yeast tropomyosin gene, designated TPM1, is present in a single copy per haploid genome and encodes a protein with a predicted molecular weight of 23.5 kd [2].
• Developmental biology. New role for tropomyosin [3].
• A new tropomyosin essential for cytokinesis in the fission yeast S. pombe [4].
• Overexpression of a second yeast tropomyosin, Tpm2p, rescues mutant phenotypes in the mdm20 strain to a lesser extent [5].

Biological context of TPM1

• Although MDM20 and TPM1 are both required for the formation and/or stabilization of actin cables, mutations in these genes disrupt mitochondrial inheritance and nuclear segregation to different extents [5].
• Loss of Tpm2p has no detectable phenotype in otherwise wild type cells, but is lethal in combination with tpm1 delta [6].
• Over-expression of Tpm2p in vivo alters the axial budding of haploids to a bipolar pattern, and this can be partially suppressed by co-over-expression of Tpm1p [6].
• Sequence analysis of chromosome IX of Saccharomyces cerevisiae revealed an open reading frame of 166 residues, designated TPM2, having 64.5% sequence identity to TPM1, that encodes the major form of tropomyosin in yeast [6].
• Here we show that TPM1 disrupted cells grow slowly, show heterogeneity in cell size, have delocalized deposition of chitin, and mate poorly because of defects in both shmooing and cell fusion [7].

Anatomical context of TPM1

• Yeast contains two genes, TPM1 and TPM2, encoding tropomyosins, either of which can provide an essential function in the yeast cytoskeleton [8].
• Many of the TPM1-deleted cells contain abundant vesicles, similar in morphology to late secretory vesicles, but without an abnormal accumulation of intermediates in the delivery of either carboxypeptidase Y to the vacuole or invertase to the cell surface [7].
• Our results imply that, in striated muscles, troponin and myosin serve to stabilize tropomyosin in inhibitory and activating states, respectively [9].
• In smooth muscle and non-muscle cells, where troponin is absent, the precise role and structural dynamics of tropomyosin on actin are poorly understood [9].
• Indirect double immunofluorescence experiments showed partial co-localization of PC2 and TM-1 in transfected mouse fibroblast NIH 3T3 cells [10].

Associations of TPM1 with chemical compounds

• Despite this, three-dimensional reconstruction of electron microscope images of filaments in the presence of troponin and Ca(2+) showed tropomyosin to be in a position similar to that found for muscle actin filaments, where most of the myosin binding site is exposed [11].
• To monitor binding of tropomyosin to yeast actin, we mutated S235 to C and labeled the actin with pyrene maleimide at both C235 and the normally reactive C374 [12].
• The mutators exhibited a variety of responses to damaging agents such as UV light and ethidium bromide; especially in a representative mutant from the complementation group tpm1, the induction of rho- mutants was sensitive to UV light and resistant to ethidium bromide.(ABSTRACT TRUNCATED AT 250 WORDS)[13]

Physical interactions of TPM1

• Despite its shorter length, Tpm2p can compete with Tpm1p for binding to F-actin [6].

Regulatory relationships of TPM1

• Tropomyosin is an extended coiled-coil protein that influences actin function by binding longitudinally along thin filaments [14].
• In striated muscle, tropomyosin regulates contractility by sterically blocking myosin-binding sites on actin in the relaxed state [9].

Other interactions of TPM1

• Synthetic lethality is also observed between mdm20 and tpm1 mutant strains [5].
• Disruption of TPM1 is not lethal but results in the loss of actin cables and confers a partial defect in polarized secretion [15].
• All other combinations of double mutations and the triple mutant lacking tropomyosin, Abp1p, and capping protein, are viable and their phenotypes are similar to or only slightly more severe than those of the single mutants [16].
• Also, synthetic lethality between anc3 and sac6 mutations, and between anc4 and tpm1 mutations was observed [17].
• The myo2-66 conditional mutation shows synthetic lethality with the TPM1 disruption, indicating that the MYO2 and TPM1 gene products may be involved in the same, or parallel function [7].

Analytical, diagnostic and therapeutic context of TPM1

• Indirect immunofluorescence microscopy reveals that tropomyosin is localized with actin cables in wild-type cells [2].
• Using electron microscopy and three-dimensional image reconstruction, the association of a diverse set of wild-type and mutant actin and tropomyosin isoforms, from both muscle and non-muscle sources, was investigated [9].
• Co-immunoprecipitation (co-IP) studies using 3T3 cells and Xenopus oocytes co-expressing PC2 and TM-1 (or TM-1a) revealed in vivo association between the protein pairs [10].

References