Saravanan, T. | Search bioRxiv

bioRxiv2025

Loss of PIKfyve in Rod Photoreceptors and RPE Cells Leads to Endolysosomal Dysfunction and Retinal Degeneration

Photoreceptor outer segment (OS) degradation is primarily mediated by retinal pigment epithelial (RPE) cells through daily phagocytosis of shed distal OS tips. In contrast, much less is understood about the cell-autonomous mechanisms photoreceptors use to clear mislocalized molecules caused by protein misfolding or trafficking defects. Mislocalized or excess rhodopsin that fails to reach the OS is retained in the inner segment or cell body, where it is presumably degraded via the endolysosomal system. We identify PIKfyve, a phosphoinositide kinase that generates PI(3,5)P2, as a key regulator of this pathway. Using Translating Ribosome Affinity Purification (TRAP), we find that PIKfyve is highly expressed in rod photoreceptors. Rod-specific PIKfyve deletion causes progressive retinal degeneration, marked by inner segment vacuolation, elevated LAMP1/2, thinning of the outer nuclear layer, and eventual loss of rod and cone function. Loss of one copy of PIKfyve in rod photoreceptors accelerates degeneration in P23H rhodopsin mutant mice. In RPE cells, PIKfyve loss disrupts phagocytosis and autophagy, leading to accumulation of rhodopsin, LAMP1, LC3A/B, and lipid droplets, along with metabolic disturbances. These findings demonstrate that PIKfyve is essential for photoreceptor and RPE health by regulating lysosomal function, phagocytosis, autophagy and metabolism, and suggest that enhancing PIKfyve activity could be a therapeutic strategy for retinal degenerative diseases.

neuroscience↗

bioRxiv2024

Dialogues in colour and behaviour - Integration of complex signalling traits and physiology

Animal communication can be complex, often involving multiple static and dynamic traits. The extent to which these traits are correlated can elucidate their function as either redundant or multiple messages. Using the agamid lizard, Psammophilus dorsalis, as a model system we examined patterns of trait expression and the role of steroid hormones in mediating these traits during social interactions. We staged male-male interactions in the lab and measured the repertoire of display behaviour and colours, which change dynamically in the visible and ultraviolet ranges in different body regions. Additionally, we measured testosterone and corticosterone levels before and after the social trials. Our results show that within behaviour and colour trait categories, components were strongly correlated within individuals, suggesting either a shared physiological pathway or redundant information content. However, across trait categories, correlation patterns varied. The chromatic contrast of the (yellow) dorsal region of lizards was correlated with both body size and level of aggression, whereas the size of UV patches was correlated with body size only. We also found a negative association between baseline corticosterone levels, body size and dorsal yellow chromatic contrast, suggesting a mechanistic link between these traits. However, social interaction induced testosterone and corticosterone levels were uncorrelated with the expression of the dynamic behavioural and colour displays during the social interactions itself. Notably, the intensity of colour and behavioural displays of males were matched by their opponents. Overall, our results suggest that multiple signalling traits can ensure both redundancy as well as provide multiple messages to receivers, thus improving the robustness of information transfer, particularly during competitions which have high fitness consequences.

animal behavior and cognition↗