BIOGENESIS AND PATHOPHYSIOLOGY OF INTRACELLULAR ORGANELLES IN MAMMALIAN CELLS

Our main interest is focused on the diverse molecular mechanisms that govern the continuous replacement andmaintenance, as well as proper functioning, of the two main biosynthetic organelles, the endoplasmic reticulum and the Golgi apparatus, in mammalian cells. Our goal is to identify novel molecular mechanisms that specifically are

1. utilized by different types of proteins for their correct localization in the ER or the Golgi apparatus, or
   
2. required for the regulation of the dynamic and unique ionic conditions and pH homeostasis in these organelles

The curious status of the Golgi apparatus in cancer cells is also one of our favorite topics, as these cells produce mainly incompletely processed glycoproteins and –lipids. We are currently characterizing the molecular defects that are responsible for these cancer-associated glycosylation abnormalities. The work in the lab utilizes modern cell biological techniques and experimental systems, and also provides a challenging atmosfere for training in cell biology. 

Group members

Sakari Kellokumpu, Ph.D., group leader
Nina Kokkonen, B.Sc.
Antti Rivinoja, B.Sc.
Annika Kauppila, lab. technician

An interested reader will find more detailed information from the following publications:

Kellokumpu, S., L. Neff, S. Jämsä-Kellokumpu, R. Kopito, and R. Baron. (1988) A 115-kD polypeptide immunologically related to erythrocyte band 3 is present in Golgi membranes. Science 242:1308-1311.

Kellokumpu, S., R. Sormunen, J. Heikkinen, and R. Myllylä. (1994) Lysyl hydroxylase, a collagen processing enzyme, exemplifies a novel class of luminally-oriented peripheral membrane proteins in the endoplasmic reticulum. J. Biol. Chem. 269:30524-30529.

Kellokumpu, S., M. Suokas, L. Risteli, and R. Myllylä. (1997) Protein disulphide isomerase and newly synthesized procollagen chains form higher-order structures in the lumen of the endoplasmic reticulum.1997. J. Biol. Chem. 272: 2770-2777.

Kellokumpu, I., L. Andersson, and S. Kellokumpu. (1997) Detection of colorectal neoplasia by peanut agglutinin (PNA)-reactive carbohydrate structures in rectal mucus. Int. J. Cancer, 74:648-653

Holappa Katja, M. Mustonen, P. Vihko, M. Parvinen, H. Rajaniemi, and S. Kellokumpu (1999). Primary structure and expression of a sperm cell anion exchanger during spermatogenesis. Biol. Reprod. 61: 981-986.

Suokas, M., Myllylä, R., and S. Kellokumpu (2000): A single C-terminal peptide segment mediates both membrane association and retention of lysyl hydroxylase in the endoplasmic reticulum. J. Biol. Chem. 275: 17863-17868.

Holappa K., M. Suokas, P. Soininen, and S. Kellokumpu (2001). Identification of the Chloride/Bicarbonate Exchanger Type 2 (AE2a) As the Golgi-Associated anion exchanger. J. Histochem. Cytochem. 49: 259-269.

Kellokumpu, S., R. Sormunen and I. Kellokumpu. (2002) Abnormal Glycosylation And Altered Golgi Structure in Colorectal Cancer: Dependence on Intra-Golgi pH. FEBS Lett. 516: 217-224.

Suokas, M., Lampela, O., Juffer, A., Myllylä, R. and S. Kellokumpu (2003) Retrieval-independent localization of Lysyl Hydroxylase in the endoplasmic reticulum via a peptide fold in its iron binding domain. Biochem. J. 370: 913-920

Holappa K.and S. Kellokumpu (2003) Targeting of the AE2 anion exchanger to the Golgi Apparatus Is Cell Type-Dependent and Correlates with the Expression of Ank195, a Golgi Membrane Skeletal protein. FEBS Lett., 546:257-64.

Alanen, H.J., Williamson, R.A., Howard, M., Lappi, A.K., Jäntti, H.P., Rautio, S.M., Kellokumpu, S. and L.W. Ruddock (2003). Functional Characterization of ERp18, a new endoplasmic reticulum located thioredoxin superfamily member. J. Biol. Chem. 278(31):28912-20.

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