Max D. Summers received his A.B. in Biology degree from Wilmington College and his Ph.D. in Entomology at Purdue University. Postdoctoral study: NSF Faculty Associate at the University of Texas at Austin. He was an Assistant/Associate Professor of Botany at the University of Texas at Austin. He is now a Distinguished Professor of Entomology at Texas A&M with joint appointments in Biology, Biochemistry and Biophysics and Genetics.

Website: www.tamu.edu/summerslab/

Max D. Summers
Distinguished Professor (Joint)

2475 TAMU
College Station, TX 77843-2475

Office:
Minnie Bell Heep Building
Room 324
979-845-9036

Lab:
Minnie Bell Heep Building
Room 324
979-845-9756

Fax: 979-845-6305
Email: m-summers@tamu.edu

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 1001 :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 ) PNAS 1001 :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.

Saksena S, Shao Y, Braunagel SC, Summers, M.D., Johnson AE. (2004) Cotranslational integration and initial sorting at the endoplasmic reticulum translocon of proteins destined for the inner nuclear membrane. Proc Natl Acad Sci U S A. 2004 Aug 24;101(34):12537-42. Epub 2004 Aug 11. PMID: 15306686

Braunagel SC, Williamson ST, Saksena S, Zhong Z, Russell WK, Russell DH, Summers MD. (2004) Trafficking of ODV-E66 is mediated via a sorting motif and other viral proteins: facilitated trafficking to the inner nuclear membrane. Proc Natl Acad Sci U S A. 2004 Jun 1;101(22):8372-7. Epub 2004 May 18. PMID: 15150405

Braunagel, S.C., Russell, W.K., Rosas-Acosta, G., Russell, D.H., and Summers, M.D. (2003) Determination of the Protein Composition of the Occlusion-Derived Virus of Autographa californica nucleopolyhedrovirus. Proc. Nat. Acad. Sci., USA/Section Biochemistry. (100): 9797-9802.

Braunagel, S.C., Guidry, P.A., Rosas-Acosta, G., Engelking, L., and Summers, M.D. (2001) Identification of BV/ODV-C42: A structural protein of Autographa californica nucleopolyhedrovirus (orf 101) is present in infected cell complexes which include ODV-EC27 and p78/83. J. Virol. 75 (24): 12331-12338.

Rosas-Acosta, G., Braunagel, S.C., and Summers, M.D. (2001) Effects of deletion and over-expression of the AcMNPV FP25K gene on the synthesis of two occlusion-derived virus envelope proteins and their transport into virus-induced intranuclear membranes of two ODV envelope proteins. J. Virol. 75: 10829-10842.

Braunagel, S.C., Guidry, P.A., Rosas-Acosta, G., Engelking, L., and Summers, M.D. (2001) Identification of BV/ODV-C42: A structural protein of Autographa californica nucelopolyhedrovirus (orf101) is present in infected cell complexes which include ODV-EC27 and p78/83. J. Virol. 75: 12331-12338.

Braunagel, S.C., J.K. Burks, G. Rosas-Acosta, R. Harrison, H. Ma, and M.D. Summers. 1999. Mutations within Autographa californica nucleopolyhedrovirus FP25K gene inhibits nuclear transport of ODV-E66. J. of Virology 73:8559-8570.

Beniya, H., S.C. Braunagel, and M.D. Summers. 1998. Autographa californica nuclear polyhedrosis virus: subcellular localization and protein trafficking of BV/ODV-E26 to plasma membrane, intranuclear membranes and viral envelopes. Virology 240:64-75.

Braunagel, S.C., R. Parr, M. Belyavsyki, and M.D. Summers. 1998. Autographa californica nuclear polyhedrosis virus infection results in Sf9 cell cycle arrest at G2/M phase. Virology 244:195-211.

Hong, T., Summers, M.D. and Braunagel, S.C. (1997) N-terminal sequences from Autographa californica nuclear polyhedrosis virus envelope proteins OVD-E66 and OVD-E25 are sufficient to direct reporter proteins to the nuclear envelope, intranuclear microvesicles and the envelope of occlusion derived virus. Proc. Nat. Acad. Sci., USA, 94(8):4050-4055.

Harrison, R.L., Jarvis, D.L. and Summers, M.D. (1996) The role of the AcMNPV 25K gene in baculovirus polh and p10 gene expression. Virology 226:34-46

Braunagel, S.C., He, H., Ramamurthy, P. and Summers, M.D. (1996) Transcription, translation, and cellular localization of three Autographa californica nuclear polyhedrosis virus structural proteins: ODV-E18, ODV-E35 and ODV-EC27. Virology 222:100-114

Braunagel, S.C., Elton, D.M., Ma, H. and Summers, M.D. (1996) Identification and analysis of an Autographa californica nuclear polyhedrosis virus structural protein of the occlusion derived virus envelope: ODV-E56. Virology 217:97-110

Harrison, R.L. and Summers, M.D. (1995) Mutations in the Autographa californica multinucleocapsid nuclear polyhedrosis virus 25 kDa protein gene result in reduced virion occulsion, altered intranuclear envelopment and enhanced virus production. J. Gen. Virology 76:1451-1459.