Disease relevance of TULP1

• 1. TULP1 and TULP2, which are expressed in the retina, make excellent candidates for these ocular diseases as a mutation within the tub gene is known to lead to early progressive retinal degeneration [1].
• However, TUB and TULP1 show a distinctly different staining pattern in the nucleus of these neurons, perhaps explaining the difference in body weight between the Tulp1 (-/-)and tubby mutant mice [2].
• The RP14 autosomal recessive Retinitis pigmentosa (arRP) locus has been mapped to a 2cM region of chromosome 6p21 [3].
• A few inner nuclear and ganglion cells are weakly TULP1-positive [4].
• Toward a better understanding of the role of TULP1 in retinal disease, its subcellular localization was sought and the TULP1 protein binding partners identified [5].

High impact information on TULP1

• Our data suggest that mutations in TULP1 are a rare cause of recessive RP and indicate that TULP1 has an essential role in the physiology of photoreceptors [6].
• TULP1 mutation in two extended Dominican kindreds with autosomal recessive retinitis pigmentosa [3].
• 3. TULP1 (the gene encoding tubby-like protein 1) is a candidate target for the disease mutation because it maps to the RP14 minimum genetic region and because a mutation in the highly homologous mouse tub gene leads to obesity, deafness and early progressive retinal degeneration [3].
• We also report that TUB, TULP1, and TULP2 map to human chromosomes 11p15.4, 6p21.3, and 19q13.1, respectively [1].
• Tub and the genes that encode three tubby-like proteins (TULP1- TULP3) form a novel, small gene family that plays an important role in maintenance and function of neuronal cells during development and post-differentiation [7].

Biological context of TULP1

• Splicing defects in both tub and another member of the gene family, TULP1 (tubby-like protein 1), lead to phenotypes of retinal degeneration in mice and humans, respectively [8].
• METHODS: Homozygotes and heterozygotes from an extended Dominican kindred with a TULP1 splice-site gene mutation (IVS14+1,G-->A) were studied clinically and with visual function tests [9].
• METHODS: Fifteen exons of the gene were screened by single-strand conformation polymorphism analysis of 7 (of 49) arRP pedigrees showing cosegregation with TULP1 locus markers [10].
• TULP1 may be involved in actin cytoskeletal functions such as protein trafficking that takes place at or near the plasma membrane from the inner segment through the connecting cilium into the outer segment of photoreceptor cells [5].
• A determination of the recognized amino acid sequence of TULP1 by the patient serum and immunohistochemical studies on the distribution of TULP1 in the retina were done in this study [11].

Anatomical context of TULP1

• RESULTS: TULP1 localizes at or near the plasma membrane and associates with the membranous fraction of COS7 cells, probably through binding phosphorylated phospholipids [5].
• TULP1-positive cells were identified by double labeling with antibodies specific for cones, rods, and astrocytes [4].
• In photoreceptor cells, actin and TULP1 colocalize at the inner segment, connecting cilium, and outer limiting membrane [5].
• CONCLUSIONS: This TULP1 splice-site mutation in homozygotes causes early-onset, severe retinal degeneration involving macular and peripheral cones and rods [9].
• CONCLUSIONS: TULP1 is a cytoplasmic protein that associates with cellular membranes and the cytoskeleton [5].

Associations of TULP1 with chemical compounds

• In addition, TULP1 partitions to the aqueous phase during Triton X-114 extraction [5].
• The physical and imaging characteristics of a number of commercially available rare earth screen/film combinations were evaluated and compared to those of conventional calcium tungstate/X-Omat RP-14 systems [12].
• A detailed examination of the scene leads us to believe that Dr Tulp was demonstrating the function of the flexor digitorum superficialis [13].
• Dr. Nicolaes Tulp, Doctor of Medicine and Praelector Anatomiae to the Amsterdam Guild of Surgeons, showed an anatomic dissection of a forearm on the corpse of an executed criminal [14].
• On the other hand, in patients undergoing TULP, while we were not able to show any significant difference with respect to plasma prolactin levels (p > 0.05) pre- and postoperatively, plasma LH levels were significantly increased during the 3-month evaluation (p < 0.05) [15].

Other interactions of TULP1

• Two of them were novel mutations in the genes TULP1 (c.1145T-->C, F382S) and CNGB1 (c.3444 + 1G-->A) [16].
• In peripheral retina at 15.4 weeks to 1 month after birth, displaced cones in the nerve fiber layer are positive for TULP1, recoverin, and blue cone opsin [4].
• No putative pathogenic sequence changes in TULP1 were observed in North American patients with comparably severe retinal phenotypes, mainly in the diagnostic category of Leber congenital amaurosis [9].

Analytical, diagnostic and therapeutic context of TULP1

• Immunoprecipitation from retinal lysate identified F-actin as a possible TULP1-binding partner [5].
• METHODS: Immunocytochemistry and subcellular fractionation were used to determine the localization of TULP1 and actin in COS7 cells and photoreceptor cells [5].
• METHODS: TULP1 was localized by immunofluorescence microscopy in human retinas, aged 8.4 fetal weeks to adult [4].
• Sequence analysis of TULP1 was also performed in unrelated patients with severe retinal degeneration from a North American clinic population [9].
• Immunoprecipitation from retinal lysates followed by liquid chromatography tandem mass spectrometry and in vitro binding assays was used to identify TULP1-binding partners [5].

References