Disease relevance of PITPNM1

• From P12, Nir2 was uniformly expressed in all classes of retinal neuronal cells, including ganglion cells, horizontal cells, amacrine cells, bipolar cells, and photoreceptor cells [1].

High impact information on PITPNM1

• Here we show that, at the onset of mitosis, Cdk1 phosphorylates the peripheral Golgi protein Nir2 at multiple sites; of these, S382 is the most prominent [2].
• Phosphorylation of Nir2 by Cdk1 facilitates its dissociation from the Golgi apparatus, and phospho-Nir2(pS382) is localized in the cleavage furrow and midbody during cytokinesis [2].
• These results indicate that Nir2 is involved in maintaining a critical DAG pool in the Golgi apparatus by regulating its consumption via the CDP-choline pathway, demonstrating the interface between secretion from the Golgi and lipid homeostasis [3].
• Nir2 colocalizes with the small GTPase RhoA in the cleavage furrow and the midbody, and it associates with RhoA in mitotic cells [4].
• In this study we provide evidence that the protein Nir2 is essential for cytokinesis [4].

Biological context of PITPNM1

• In order to facilitate the analysis of these genes we have used radiation hybrid mapping and fluorescence in situ hybridization to localize the PITPNM2 and 3 genes to human chromosomes 12p24 and 17p13 respectively and hybrid mapping to confirm the localization of PITPNM1 to chromosome 11q13 [5].
• Depletion of Nir2 by RNAi leads to substantial inhibition of protein transport from the trans-Golgi network to the plasma membrane, and causes a reduction in the DAG level in the Golgi apparatus [3].
• Immunolocalization studies revealed that Nir2 is mainly localized in the Golgi apparatus in interphase cells, but it is recruited to the cleavage furrow and the midbody during cytokinesis [4].
• Nir2, a novel regulator of cell morphogenesis [6].
• Targeting of Nir2 to lipid droplets was attributed to its enhanced threonine phosphorylation [7].

Anatomical context of PITPNM1

• In the adult rat retina, Nir2 was preferentially localized to the somata of all classes of retinal neurons, whereas Nir3 was highly expressed in the synaptic terminals [1].

Associations of PITPNM1 with chemical compounds

• These results suggest that a specific threonine within the PI-transfer domain of Nir2 provides a regulatory site for targeting to lipid droplets [7].
• However, oleic-acid treatment caused translocation of wild-type Nir2, but not translocation of the T59A mutant, to lipid droplets [7].
• The decay of NIR1 leads to NIR2, which is attributed to the carotenoid radical cation [8].
• We hypothesized that modification of folate would retain receptor affinity in vivo, despite the bulkier NIR fluorochrome, NIR2 (em = 682 nm) [9].

Other interactions of PITPNM1

• We provide evidence that Nir (Nir1, Nir2, and Nir3)-VAP-B interactions are mediated through the conserved FFAT (two phenylalanines (FF) in acidic tract) motif present in Nir proteins [10].
• We also show that the Nir2-VAP-B interaction attenuates protein export from the ER [10].

Analytical, diagnostic and therapeutic context of PITPNM1

• Microinjection of anti-Nir2 antibodies into interphase cells blocks cytokinesis, as it results in the production of multinucleate cells [4].

References