Conservation of Tubulin-Binding Sequences in TRPV1 throughout Evolution

Abstract

Background Transient Receptor Potential Vanilloid sub type 1 (TRPV1), commonly known as capsaicin receptor can detect multiple stimuli ranging from noxious compounds, low pH, temperature as well as electromagnetic wave at different ranges. In addition, this receptor is involved in multiple physiological and sensory processes. Therefore, functions of TRPV1 have direct influences on adaptation and further evolution also. Availability of various eukaryotic genomic sequences in public domain facilitates us in studying the molecular evolution of TRPV1 protein and the respective conservation of certain domains, motifs and interacting regions that are functionally important. Methodology and Principal Findings Using statistical and bioinformatics tools, our analysis reveals that TRPV1 has evolved about ∼420 million years ago (MYA). Our analysis reveals that specific regions, domains and motifs of TRPV1 has gone through different selection pressure and thus have different levels of conservation. We found that among all, TRP box is the most conserved and thus have functional significance. Our results also indicate that the tubulin binding sequences (TBS) have evolutionary significance as these stretch sequences are more conserved than many other essential regions of TRPV1. The overall distribution of positively charged residues within the TBS motifs is conserved throughout evolution. In silico analysis reveals that the TBS-1 and TBS-2 of TRPV1 can form helical structures and may play important role in TRPV1 function. Conclusions and Significance Our analysis identifies the regions of TRPV1, which are important for structure – function relationship. This analysis indicates that tubulin binding sequence-1 (TBS-1) near the TRP-box forms a potential helix and the tubulin interactions with TRPV1 via TBS-1 have evolutionary significance. This interaction may be required for the proper channel function and regulation and may also have significance in the context of Taxol®-induced neuropathy.

Thermosensitive ion channel TRPV1 is endogenously expressed in the sperm of a fresh water teleost fish (Labeo rohita) and regulates sperm motility

“…For example, endogenous expression of TRPV1 in boar spermatozoa has been linked with endocannabinoid and anandamide signaling, which have implications in capacitation and acrosomal reaction. 24,25 In case of human also, endogenous expression of TRPV1 has been detected in sperm and linked with sperm functions. In human sperm cells, both hot and cold-sensitive TRP ion channels are present and regulate several functions related to motility and fertility.…”

Use of von Frey filaments to assess nociceptive sensitization in the hornworm, Manduca sexta

“…The conserved nature of pain receptors such as the TRP receptors (e.g. Kim et al ., 2012; Saito et al ., 2012; Sardar et al ., 2012; Palovcak et al ., 2015), and associated signal transduction machinery (e.g. Lin et al ., 1997; Lewin and Walters, 1999; Nikitin and Kozyrev, 2000) suggest that such a model will be invaluable in this field of research.…”

TRPV1–tubulin complex: involvement of membrane tubulin in the regulation of chemotherapy‐induced peripheral neuropathy

“…Interestingly, these two stretch sequences contain positively charged residues that are conserved throughout evolution (Sardar et al . ). These two stretch sequences from different species suggest that these regions of TRPV1 can form putative alpha helical structures projecting the positive‐charged residues at one side of the helix.…”