Shroom2 (APXL) regulates melanosome biogenesis and localization in the retinal pigment epithelium

Abstract

Shroom family proteins have been implicated in the control of the actin cytoskeleton, but so far only a single family member has been studied in the context of developing embryos. Here, we show that the Shroom-family protein,Shroom2 (previously known as APXL) is both necessary and sufficient to govern the localization of pigment granules at the apical surface of epithelial cells. In Xenopus embryos that lack Shroom2 function, we observed defects in pigmentation of the eye that stem from failure of melanosomes to mature and to associate with the apical cell surface. Ectopic expression of Shroom2 in naïve epithelial cells facilitates apical pigment accumulation, and this activity specifically requires the Rab27a GTPase. Most interestingly, we find that Shroom2, like Shroom3 (previously called Shroom),is sufficient to induce a dramatic apical accumulation of the microtubule-nucleating protein γ-tubulin at the apical surfaces of naïve epithelial cells. Together, our data identify Shroom2 as a central regulator of RPE pigmentation, and suggest that, despite their diverse biological roles, Shroom family proteins share a common activity. Finally,because the locus encoding human SHROOM2 lies within the critical region for two distinct forms of ocular albinism, it is possible that SHROOM2mutations may be a contributing factor in these human visual system disorders.

Synteny and candidate gene prediction using an anchored linkage map of Astyanax mexicanus

“…S1 C, red). Finally, our sequence analysis was least successful in the current draft of the Tetraodon genome with five linkage groups (15,17,25,27,28) returning no hits from this species (Fig. S1 D, gray).…”

“…S3). This was intriguing, because Shroom2 plays an essential role in regulating the biogenesis and localization of melanin in the developing retina (27). Further, the Shroom2 locus lies within a crucial genomic region of two forms of ocular albinism in humans, possibly contributing to visual system disorders.…”

Shroom family proteins regulate γ-tubulin distribution and microtubule architecture during epithelial cell shape change

“…Moreover, Shroom1 and also another family member, Shroom2, can each drive apical accumulation of ␥-tubulin, but neither can elicit significant actin assembly or apical constriction (Fig. 10A) (Fairbank et al, 2006). Finally, Shroom3 drives both apical constriction and cell elongation, and these two cell shape changes can occur independently in both RESEARCH ARTICLE Development 134 (7) neural and cement gland epithelial cells ( Fig.…”

Identification of the TFII-I family target genes in the vertebrate genome

“…Another two newly identified targets, Cfl-1 and Shrm, members of cofilin and shroom families, have been implicated in the control of actin cytoskeleton (21,22). Shrm localizes to the apical tip of adherens junctions of neural ectoderm cells and works through myosin II to regulate apical construction (23,24), the process essential for neural tube closure.…”