Tip‐1 induces filopodia growth and is important for gastrulation movements during zebrafish development

Abstract

Wnt signaling is essential during animal development and also plays important roles in pathological conditions. Two mayor pathways have been described: the β-catenin-dependent canonical (or classical) pathway and the β-catenin-independent non-canonical Wnt pathway. Recent binding studies suggest links between the small PDZ protein TIP-1 (Tax-1 interacting protein) to components of both Wnt pathways. We have cloned and characterized the zebrafish tip-1 gene. Whole mount in situ hybridization and semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) indicated that zebrafish tip-1 is present as a maternal RNA and is ubiquitously expressed during early development. After 24 h of development, tip-1 expression was high in the central nervous system (CNS) whereas only weak expression was detected in the caudal regions of the zebrafish embryo. Tip-1 knockdown using antisense morpholino oligonucleotides, as well as ectopic tip-1 expression, led to elongation defects in zebrafish embryos and larvae. Both knockdown and overexpression of tip-1 resulted in a widened goosecoid (gsc) expression domain in shield stage embryos, led to an abbreviated prechordal plate, and to reduced convergent extension movements during gastrulation. We constructed a green fluorescence protein (GFP)/TIP-1 fusion protein which, when expressed in cultured fibroblasts (ZF4-cells), induced filopodia growth. Our observations indicate a role for TIP-1 in gastrulation movements and in filopodia growth induction.

Expression of Tax-interacting protein 1 (TIP-1) facilitates angiogenesis and tumor formation of human glioblastoma cells in nude mice

“…TIP-1 is conserved protein across several species [6]. In zebrafish, high level of TIP-1 expression was detected in the early stage of embryo development and only in central nervous system thereafter.…”

“…In zebrafish, high level of TIP-1 expression was detected in the early stage of embryo development and only in central nervous system thereafter. TIP-1 inhibition impaired the filopodia growth and gastrulation movement [6]. In mammals, TIP-1 expression was detected in both of neurons and astrocytes though the roles of TIP-1 expression in these cells have not been defined yet [32].…”

“…TIP-1, also known as Tax1-binding protein 3 (Tax1bp3) and glutaminase-interacting protein (GIP), is a small (124 amino acids in human and mouse) and conserved protein containing single PDZ (PSD-95/DlgA/ZO-1) domain [6]. TIP-1 involves in a wide spectrum of biological processes through selective protein interactions, such as beta-catenin [7], brain-specific angiogenesis inhibitor 2 [8], rhotekin [9], HPV16 E6 [10], HTLV-1 Tax [11], ARHGEF16 [12], potassium channel Kir2.3 [13], and glutaminase [14].…”

“…TIP-1 involves in a wide spectrum of biological processes through selective protein interactions, such as beta-catenin [7], brain-specific angiogenesis inhibitor 2 [8], rhotekin [9], HPV16 E6 [10], HTLV-1 Tax [11], ARHGEF16 [12], potassium channel Kir2.3 [13], and glutaminase [14]. TIP-1 has been reported to regulate gastrulation movements during zebrafish embryo development [6]. In Madin-Darby canine kidney (MDCK) cells, TIP-1 modulates trafficking of intracellular proteins and contributes to the establishment of cell polarity [13].…”

Anti-tax interacting protein-1 (TIP-1) monoclonal antibody targets human cancers

“…A single PSD-95/DlgA/ZO-1 (PDZ) domain (89 amino acids) is the only structural and functional unit in the small protein (total of 124 amino acids in human and mouse), distinguishing TIP-1 from other PDZ proteins. TIP-1 functions as a scaffold for protein complex assembly and is highly conserved across species [8]. TIP-1 plays an important role in cancer, directly or indirectly regulating various signaling pathways that are involved in cancer development and progression.…”