Max D. Summers

Title*:  Distinguished Professor, Holder, Endowed Chair in Agricultural Biotechnology

Education:

• A.B. Biology, Wilmington College, 1962
• Ph.D. Entomology, Purdue University, 1968

Courses Taught: Entomology 609; Insect Microbiology; Biology

Research Emphasis: Baculovirus-host interactions, molecular biology of virion maturation in the nucleus of cells.

Viral and Cellular Mechanisms of Integral Membrane Protein Sorting to the Inner Nuclear Membrane and Viral Induced Nuclear Membranes

Our research addresses the mechanism(s) of integral membrane protein sorting and trafficking to the eukaryote cell inner nuclear membrane, and to viral-induced intranuclear membranes. This is important because mutations in a number of inner nuclear membrane proteins correlate with several human diseases including muscular and lipid dystrophies. In eukaryotes, the nucleus is delimited by the nuclear envelope (NE), which consists of an outer nuclear membrane (ONM) and an inner nuclear membrane (INM) separated by a lumen, and penetrated by nuclear pore complexes. The current model for protein sorting to the INM states that integral proteins diffuse between the continuous membrane of the endoplasmic reticulum (ER) and the membranes of the NE, and are selectively retained at the INM by binding with nuclear factors such as protein or DNA.

We study the sorting of baculovirus envelope proteins that transit from their site of insertion in the ER, to the ONM and INM. These finally target to viral induced vesicle precursors which to form in the nucleoplasm and become the viral envelope. To identify potential regulatory and/or sorting factors that function during viral infection, several virus envelope proteins were studied for interactions with translocon proteins during integration. We show by comparing photocrosslinking of viral and INM cellular proteins through the translocon, that both viral and cellular transmembrane sequences (TMSs) occupy a similar location in the translocon, yet occupy different sites than do non-INM directed TMSs. These results provide evidence that: 1) INM directed TMSs are initially recognized and sorted at the translocon (a proposed new role for ER translocons); and, 2) for some integral membrane proteins, sorting to the nucleus may be an active process involving specific non-nuclear proteins [Saksena et al. (2004) PNAS 101:12537].

Our studies also demonstrate that sorting of a viral envelope protein to the INM is mediated by a specific INM-sorting motif (INM-SM). The INM-SM consists of the 33 N-terminal amino acids which contain a TMS and associated charges resulting in a specific orientation within the membrane [Braunagel et al. (2004) PNAS101:8372-8377]. Using site-specific crosslinking it was demonstrated following ER membrane integration, that the INM-SM is adjacent to two viral proteins; and the deletion of one of these proteins results in inefficient sorting of an integral membrane viral protein to nuclear membranes. With the observation that viral proteins may specifically facilitate viral envelope protein sorting to nuclear membranes, we speculate that in normal cells specific cellular proteins may function to facilitate sorting and trafficking. Using similar crosslinking experiments with the same INM-SM integration intermediates, we are testing for INM-SM proximity to cellular proteins that may facilitate the sorting of integral proteins in transit to the INM. Our studies now provide evidence that the co-translational integration and sorting of viral envelope proteins is a protein-facilitated and protein-regulated multistep process which may also be utilized during sorting of cellular INM directed proteins. Check our 2004 publications for details.

Selected Publications