In addition to its location at the border of the nucleus, nuclear protein lamin B2 was found right near the boundary of the nucleolus, as well. Besides playing an important role in maintaining the structure and function of the nucleus, lamin B2 also determines the morphology and function of the nucleolus.

For the first time, nuclear protein lamin B2, which is well known to play an important role in maintaining the structure and function of the nucleus, has been found to determine the morphology and function of the nucleolus, a roundish entity found inside the nucleus. The nucleolus makes ribosomal ribonucleic acid (rRNA) and ribosomes. Like in the case of the nucleus, the lamin B2 protein is found at the border of nucleolus, which is again a new finding.

In contrast to normal cells that contain one or two spherical and regular-shaped nucleoli, cancer cells may have as many as 10. Cancer cells are highly proliferative in nature and require more protein synthesis for survival. The demand for additional protein in cancerous cells is met by large-sized nucleoli that are distorted in shape or by nucleoli which are found in abundance. Cancer cells can also have large number of nucleoli that are large-sized.

Peering deep into cells using a super resolution microscope, a two-member team led by Kundan Sengupta from the Indian Institute of Science Education and Research (IISER) Pune found that in addition to their location at the border of the nucleus, lamins were found right near the boundary of the nucleolus, as well. “We were able to locate lamin B2 at the border of nucleolus as we isolated the nucleolus from the cell and used antibody staining to identify lamin B2,” says Dr. Sengupta. “Since lamins’ role in controlling the shape and function of the nucleus is well known, we wanted to determine if they played a similar role in the case of the nucleolus too.” Dr. Sengupta is an Intermediate Fellow of the Wellcome Trust/DBT India Alliance.

Using a molecular approach, the researchers reduced the levels of lamin B2 in colorectral cancer cell lines. “In about 75% of the cancer cells the nucleoli lost their shape and came together to form a large aggregate,” says Ayantika Sen Gupta from IISER Pune and first author of a paper published in the journal Molecular and Cellular Biology. The aggregate occupied more volume than when the nucleoli were present as separate entities. When the lamin B2 was restored to its normal level, the nucleoli regained their original, discrete shape. “This strongly suggests that lamin B2 controls the shape of the nucleolus,” says Ms. Sen Gupta.

Besides affecting the shape of the nucleolus, lamin B2 controls the function of the nucleolus. When lamin B2 level was depleted, there was an increase in the expression levels of 45 pre-rRNAs. Lamin B2 also modulates the entry and exit of nucleolin protein, which is a biomarker for cancer. Nucleolin protein also forms an aggregate when nucleoli lose their shape when B2 level is depleted.

Published in The Hindu on January 30, 2018