TCTEX1D4 Interactome in Human Testis: Unraveling the Function of Dynein Light Chain in Spermatozoa

Abstract

Studies were designed to identify the TCTEX1D4 interactome in human testis, with the purpose of unraveling putative protein complexes essential to male reproduction and thus novel TCTEX1D4 functions. TCTEX1D4 is a dynein light chain that belongs to the DYNT1/TCTEX1 family. In spermatozoa, it appears to be important to sperm motility, intraflagellar transport, and acrosome reaction. To contribute to the knowledge on TCTEX1D4 function in testis and spermatozoa, a yeast two-hybrid assay was performed in testis, which allowed the identification of 40 novel TCTEX1D4 interactors. Curiously, another dynein light chain, TCTEX1D2, was identified and its existence demonstrated for the first time in human spermatozoa. Immunofluorescence studies proved that TCTEX1D2 is an intra-acrosomal protein also present in the midpiece, suggesting a role in cargo movement in human spermatozoa. Further, an in silico profile of TCTEX1D4 revealed that most TCTEX1D4 interacting proteins were not previously characterized and the ones described present a very broad nature. This reinforces TCTEX1D4 as a dynein light chain that is capable of interacting with a variety of functionally different proteins. These observations collectively contribute to a deeper molecular understanding of the human spermatozoa function.

Actl7b-deficiency leads to mislocalization of LC8 type dynein light chains and disruption of murine spermatogenesis

“…Other dynein light chains have been described in spermatogenesis. For the dynein light chain tctex-type 4 (DNLT4), 40 different interactors have been identified in human testis, showing the functional variety of dynein light chain interacting proteins (Freitas et al, 2014). In human, absence or lower levels of dynein light chain tctex-type 1 (DNLT1), have been associated with male infertility (Indu et al, 2015).…”

Intraflagellar Protein 88 Interactome Analysis: A Bioinformatics Approach Highlights Its Role in Testis and Sperm Function

“…IFT88 interactome was retrieve from several databases and TCTEX1D4 was added to the interactome since IFT88 was identified as a TCTEX1D4 interactor [14]. Most interactors were identified by indirect methods; therefore these interactions must be confirmed by direct methods.…”

“…Recently, IFT88 has also been linked to migration and invasion of hepatoma cells [11], to olfactory function [12], spindle formation [8], and to mitosis (a non-cilium function) [13]. Recently a yeast two hybrid screen performed in our laboratory revealed that, in testis, IFT88 interacts with TCTEX1D4 (t-complex testis expressed 1 domain containing 4), a dynein light chain from the DYNT1/TCTEX1 family [14]. TCTEX1D4 was first described as an interactor of several components of the TGFbeta pathway [15].…”

Consensus nomenclature for dyneins and associated assembly factors

“…This gene encodes a dynein light chain protein that belongs to the TCTEX1 family. Freitas et al (2014) discussed its role in sperm motility and IFT.…”