Dynamin- and Rab5-dependent endocytosis is required to preventDrosophilaphotoreceptor degeneration

Abstract

In Drosophila photoreceptors, Rhodopsin 1 (ninaE, Rh1) is required for proper morphogenesis and maintenance of the apical light-gathering organelle, the rhabdomere. It has been proposed that Rh1, coupled to the Rho GTPases Rac1 and Cdc42, promotes the morphogenesis of a sub-rhabdomeric F-actin meshwork or rhabdomere terminal web (RTW). The RTW provides mechanical support to the apical microvilli and is likely to guide Rab11-dependent delivery of Rh1-rich membrane to the rhabdomere from the trans Golgi network. However, the nature and function of the molecular pathway involved in RTW morphogenesis remains incomplete. Here, we show that Rh1 function in promoting RTW morphogenesis is light-independent and is conserved throughout evolution. This Rh1 function does not require Gqαe, which is required for phototransduction. Finally, we show that interfering with Dynamin- and Rab5-dependent endocytosis leads to a phenotype that is undistinguishable from that of the ninaE-null mutant. Importantly, the corresponding endocytic activity is essential to prevent early onset of rhabdomere degeneration. In conclusion, we propose that Rh1 function in promoting RTW morphogenesis is not only needed to sustain apical membrane delivery but is also required for proper rhabdomeric membrane endocytosis and turnover.

Ectopic Expression of Mouse Melanopsin in Drosophila Photoreceptors Reveals Fast Response Kinetics and Persistent Dark Excitation

“…1B, left), showing deformed structure. Nevertheless, the increase in rhabdomere diameter in opn4;ninaE I17 flies relative to the ninaE I17 mutant indicates some rescue of the rhabdomeral size and shape by OPN4 expression, as reported previously for ectopically expressed human melanopsin in Drosophila R1-6 cells (30).…”

“…However, they failed to observe functional expression of OPN4 in adult flies (23,30). This failure, most likely, resulted from the use of the insensitive ERG signal to monitor functional expression of OPN4 (e.g.…”

Rhodopsin homeostasis and retinal degeneration: lessons from the fly

“…Besides its light-sensing function, Rh1 is required for maintaining the structure of rhabdomeres. Rh1 is an essential component of the rhabdomere terminal web (RTW), an F-actin meshwork that provides a mechanical force to support the rhabdomeric membranes and mediates vesicular trafficking towards rhabdomeres [24, 25]. Hence, complete loss of Rh1 leads to collapse of rhabdomeres and partial loss of Rh1 leads to formation of smaller rhabdomeres [26–29].…”

“…However, loss of arr1 leads to a light-independent retinal degeneration [82], suggesting that Arr1 mediates other functions than Mrh endocytosis. Similarly, inhibition of Mrh endocytosis using a temperature-sensitive Dynamin ( Shibire ts ) or a dominant negative Rab5 induces retinal degeneration [24]. However, in some contexts, inhibiton of endocytosis delays degeneration, an issue that will be discussed later.…”

σ2-Adaptin Facilitates Basal Synaptic Transmission and Is Required for Regenerating Endo-Exo Cycling Pool Under High-Frequency Nerve Stimulation in Drosophila

“…One such example is the disruption of the rhabdomere base when shi ts flies are grown at restrictive temperature for 4 hr (Pinal and Pichaud 2011). Rh1-Gal4-driven shi ts1 flies raised at 19°led to an enlargement of photoreceptor cell bodies with the interrhabdomeric space being reduced (Gonzalez-Bellido et al 2009).…”