Fellow’s Research: It takes two to tango—partnership of two nuclear proteins maintains organisation and function of our genome
10 Jul 2019
Dr Kundan Sengupta, Intermediate Fellow
Indian Institute of Science Education and Research, Pune
Our recently published work provides insights into the role of two major nuclear proteins— Lamin A and Emerin—in maintaining organization and function of our genome.
The nucleus is the control center of our cells as it houses our genetic material. Our genome, within the nucleus, is protected from external assaults by a double layered membrane, the nuclear envelope. The nuclear envelope associates with various proteins, including the nuclear lamins that confer mechanical and structural stability to the nucleus. The protein Lamin A is predominantly present at the nuclear envelope, and it associates with another protein, Emerin. Together, Lamin A and Emerin act as molecular gatekeepers to regulate and relay signals from outside into the nucleus and into DNA, for proper cell function.
Each of our 46 chromosomes occupy a distinct space in the nucleus referred to as the ‘chromosome territory’. While the rules that dictate where a chromosome territory should reside inside the nucleus are not completely understood, it is well established that chromosomes with more genes (i.e. gene-dense chromosomes) are generally located in the nuclear interior, while gene-poor chromosomes are closer to the nuclear envelope. We asked if Lamin A and Emerin had a role to play in this organization of chromosomes in the nucleus?
We found that, in cancer cell, lowering levels of either Lamin A or Emerin alone does not appreciably perturb the locations of chromosome territories in the nucleus. However, lowering both Lamin A and Emerin together, considerably changes chromosome positions in the nucleus. Additionally, to understand the underlying mechanisms that control chromosome positions and function, we examined two other partners of Lamin A and Emerin: Actin—a protein that confers stability and shape to the cell and Nuclear Myosin I (NM1)—a motor protein in the nucleus. Interestingly, the loss of Lamin A and Emerin distinctively altered levels and location of Actin and NM1.
In summary, our study provides new information that underscores the importance of certain proteins and their interactions in the nucleus for maintaining the organization and function of chromosomes and a cell’s overall structure.
Figure: Schematic representation showing the network of Actin, Emerin and Lamins and their role in regulating the locations of chromosome territories in the nucleus. Inset: (Top): Nuclear MyosinI (NM1) labelled in green, exists as a dense fibrous network outside the nucleus and as punctate foci in the nucleus. Emerin (red) is at the nuclear border, and the nucleus is labelled with DAPI (blue). (bottom): Lowering the levels of Lamin A/C in cells increases the numbers of NM1 foci in the nucleus.
Lamin A/C and Emerin depletion impacts chromatin organization and dynamics in the interphase nucleus. Devika Ranade, Roopali Pradhan, Muhunden Jayakrishnan, Sushmitha Hegde and Kundan Sengupta. BMC Molecular and Cell Biology, May 2019