Kinesin-mediated axonal transport of a membrane compartment containing beta-secretase and presenilin-1 requires APP. - AlzForum Alzheimer Research Paper of the Week


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Annotation

	Kamal A, Almenar-Queralt A, LeBlanc JF, Roberts EA, Goldstein LS. Kinesin-mediated axonal transport of a membrane compartment containing beta-secretase and presenilin-1 requires APP. Nature. 2001 Dec 6;414(6864):643-8. PubMed Abstract, View on AlzSWAN Corresponding Author: L. Goldstein

	Comments on Paper and Primary News

	Primary News: Suspects for Aβ Generation Spotted Together, En Route to Nerve Terminal Comment by: Yong Shen
	Submitted 11 December 2001 \| Permalink	Posted 11 December 2001
	This careful study rigorously tests a creative concept. We have also detected BACE and APP, though not PS-1, in the same subcellular compartment in AD neurons. That APP, BACE and PS1 are colocalized at the same subcellular site in axons is intriguing and helpful to explain some important issues, but the axonal membrane compartment may not be only major site for Aβ generation (we found one or two sites in AD neurons). While sciatic nerve is a simple, good model to test this working hypothesis, it is also important to keep in mind that sciative nerve nerve cells differ from neurons in the brain, especially cortical or hippocampal neurons. The authors use corpus callosum as an axonal model, however, hippocampal or enthorinal cortex neurons may also be worth pursuing. They all contain neuronal cell bodies and their axonal projections and are pathologically affected areas in AD. This is a very good paper. View all comments by Yong Shen

	Primary News: Suspects for Aβ Generation Spotted Together, En Route to Nerve Terminal Comment by: Benjamin Wolozin, ARF Advisor (Disclosure)
	Submitted 11 December 2001 \| Permalink	Posted 11 December 2001
	Despite intensive study the functions of APP are unknown, however an increasing number of experiments are identifying functions of APP. This paper is interesting because it identifies a function that appears to be dependent on APP which, if true, would be a major function of APP and further the understanding of its basic biology. View all comments by Benjamin Wolozin

	Comment by: Benjamin Wolozin, ARF Advisor (Disclosure)
	Permalink
	I recommend this paper Despite intensive study the functions of APP are unknown, however an increasing number of experiments are identifying functions of APP. This paper is interesting because it identifies a function that appears to be dependent on APP which, if true, would be a major function of APP and further the understanding of its basic biology." - Benjamin Wolozin. View all comments by Benjamin Wolozin

	Comment by: shen chengyong
	Submitted 31 August 2004 \| Permalink	Posted 1 September 2004
	I recommend this paper This paper provided us with a new function mechanism of APP, which may give us some clues as to how to decrease amyloid peptide while not disturbing the normal function of. View all comments by shen chengyong

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REAGENTS/MATERIAL:
For western blots: the Klc (63-90 and Klc1), Kif5b, APP (22C11), APP (4G8), tubulin, dynein intermediate chain (Dic), Kif3a, synaptotagmin, synaptophysin and Gap43 antibodies were used.

Additional antibodies used for western blots: APP C-terminal (Chemicon), synapsin-I (Stressgen), Cox1 (Molecular Probes), A[beta]40 (Chemicon) or A[beta]42 (Chemicon), TrkA (Research Diagnostics; this antibody may cross-react with TrkB and TrkC), neurofilament-H (Smi-31, Sternberger), Bace goat polyclonal (Bace1, Chemicon), Bace1 rabbit polyclonal (Oncogene), Bip (Grp78) (Stressgen) and Pdi (Affinity Bioreagents).

The N-terminal presenilin-1 (NT) antibody, and the Aplp1 (Ct11) and Aplp2 (D2II) antibodies were provided by S. Sisodia. Presenilin-1 polyclonal antibody (Chemicon) gave the same results as the NT antibody from S. Sisodia; all blots shown are for NT.

For immunofluorescence staining: APP C-terminal (Chemicon), Bace goat polyclonal (Chemicon), presenilin-1 (NT), and Cox1 (Molecular Probes) antibodies were used. In general, samples were analysed by Tris-glycine SDS-PAGE and western blots; for the A[beta] blots, Tris-tricine gels were used.

Sciatic nerves, DRGs or corpus callosum from three pairs of age-matched nonlittermate wild-type and APP-null mutant mice 17 were dissected. For double-ligation experiments, sciatic nerves of wild-type mice were ligated at the most accessible proximal and distal ends simultaneously