High impact information on TMOD3

• We describe here a previously uncharacterized tropomodulin (Tmod) isoform, Tmod3, which is widely expressed in human tissues and is present in human microvascular endothelial cells (HMEC-1) [1].
• These data collectively demonstrate that capping of actin filament pointed ends by Tmod3 inhibits cell migration and reveal a novel control mechanism for regulation of actin filaments in lamellipodia [1].
• Tmod3 is present in sufficient quantity to cap pointed ends of actin filaments, localizes to actin filament structures in HMEC-1 cells, and appears enriched in leading edge ruffles and lamellipodia [1].
• Conversely, decreased expression of Tmod3 by RNA interference leads to faster average cell migration, along with increases in free pointed and barbed ends in lamellipodial actin filaments [1].
• Subsequent tryptic digestion and liquid chromatography/tandem mass spectrometry revealed two binding interfaces on actin, one distinct from other actin monomer binding proteins, and two potential binding sites in Tmod3, which are independent of the previously characterized leucine-rich repeat structure involved in pointed end capping [2].

Biological context of TMOD3

• Transient overexpression of GFP-Tmod3 leads to a depolarized cell morphology and decreased cell motility [1].
• These 5'-untranslated regions normally make up the first exons of two ubiquitously expressed genes clustered in chromosome 15q21.2-3 in the following order (from telomere to centromere): FLJ, TMOD3, and aromatase [3].
• Analysis of Tmod3 effects on kinetics of actin polymerization and steady state monomer levels revealed that Tmod3, unlike previously characterized tropomodulins, sequesters actin monomers with an affinity similar to its affinity for capping pointed ends [2].

Regulatory relationships of TMOD3

• These data suggest that the Tmod3 isoform may regulate actin dynamics differently in cells than the previously described tropomodulin isoforms [2].

Other interactions of TMOD3

• The aromatase gene is normally transcribed in the direction opposite to that of TMOD3 and FLJ [3].

References