Figure 1. Staining of TOR1AIP1 (green) labeling the nuclear membrand and microtubules in A-431 cells.

Figure 2. Staining of TOR1AIP1 (green) with DNA (blue) and microtubules (red) in A-431 cells. Here, overlap of red and green appear as yellow.

It's time for another HPA image of the week! This week we interrupt our series of organelle highlights to bring you another great image brought to us by the citizen scientists in Project Discovery, and specifically by x Truf a member of the Signal Cartel in EVE online who found this image while playing Project Discovery. This is x Truf's second contribution to our image of the week, and we'd like to give special thanks for these contributions!

The protein stained in Fig 1. is an image of Torsin A interacting protein 1 (TOR1AIP1, also known as LAP1). This staining shows signal specific to both the nuclear membrane and microtubules. This staining of TOR1AIP1 is in A-431 cells, human epidermoid carcinoma, however this phenotype is visible for all three cell types stained for the antibody (HPA047151).

TOR1AIP1 is a known nuclear membrane protein that is thought to localize primarily to the inner side of the nuclear membrane (Holmer & Worman 2001). This protein is a member of the torsion A complex which has been shown to be crucial for maintaining the nuclear membrane integrity. During cellular division (mitosis), this membrane breaks down as the two copies of chromosomes are separated into the two daughter cells whereupon the nuclear membrane reforms. Time-lapse microscopy has revealed that TOR1AIP1 is necessary for this process to proceed properly (Neumann et al. 2010).

In recent years, interest in this gene has piqued because of its essential role. Recent studies have revealed that mutations in this gene lead to a number diseases affecting a variety of tissues including muscular dystrophy, cerebellar atrophy, and cardiomyopathy (Kayman-Kurekci et al. 2014, Dorboz et al. 2014).

One striking attribute about this particular staining is the colocalization of this antibody with microtubules in addition to the known nuclear membrane location. This colocalization is seen in all three cell types for this experiment, but is not seen in the sibling antibody, which are compared here. In previous studies, TOR1AIP1 (called LAP1 in this study) has been shown to co-localize with microtubles in the mitotic spindle (Santos et al. 2014). To our knowledge however, colocalization of TOR1AIP1 with microtubules has not been previously reported for non-mitotic (interphase) cells.

There are two possible explanations for this additional localization. First, it is possible that TOR1AIP1 has a novel role involving interactions with the microtubles during interphase not previously reported. This could be caused by one of TOR1AIP1's several "flavors", (officially called "isoforms"), which are a result of alternative splicing events where different parts of the protein are combined to form slightly different versions of the protein. The other, less optimistic possibility is that this colocalization is a result of off-target binding of the antibody. Additional studies such as siRNA knockdowns are needed to distinguish these possibilities.

The thought that this sample may indicate a novel role for TOR1AIP1 and that it was discovered by the citizen scientists playing Project Discovery is indeed exciting, though again further validation is needed. We'd like to again extend out thanks to the all the citizen scientists participating in Project Discovery and particularly to x Truf & the Signal Cartel for once again bringing us a fantastic image and for their contribution to science!